Surbhi Sidana, MD

All Publications

• Clinical Outcomes After Idecabtagene Vicleucel in Older Multiple Myeloma Patients: A Multicenter Real-world Experience. Blood advances Kalariya, N., Hildebrandt, M. A., Hansen, D. K., Sidana, S., Khouri, J., Ferreri, C. J., Doyle, W. N., Castaneda Puglianini, O. A., Freeman, C. L., Hovanky, V., Hosoya, H., Shune, L., Patel, K. K. 2024

  Abstract

  The safety and efficacy of CAR T-cell therapy is not well described in older patients, a population that has higher frailty and co-morbidities. In this multicenter retrospective study, we evaluated clinical outcomes along with frailty and geriatric characteristics such as comorbidities, polypharmacy, falls, neuropathy, organ dysfunction, and performance status in younger (<65 years) versus older (≥65 years) patients who received commercial idecabtagene vicleucel (ide-cel). A total of 156 patients (n=75, ≥65 years) were infused with ide-cel by data cut-off. In older patients (median age: 69 years, range: 65-83 years; 66.7% frail; 77.3% did not meet KarMMa eligibility criteria), with a median follow-up duration of 14.2 months, best overall response rate (ORR) was 86.7%, which was comparable to pivotal KarMMa study results (ORR: 73%). Median progression-free survival (PFS) and overall survival (OS) in older patients were 9.1 months and 26.5 months, respectively. Grade 3 or higher cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were observed in 1% and 4% of older patients, respectively. Compared to younger patients, the older patients had significantly higher prevalence of frailty, geriatric characteristics such as polypharmacy (5+ drugs; 97%), 4+ comorbidities (69%), and organ dysfunction (35%) (p<0.05). The safety and efficacy of ide-cel therapy were similar in younger and older patients. Frailty and geriatric characteristics such as polypharmacy, comorbidities, and organ dysfunction in older patients did not confer an inferior overall outcome.

  View details for DOI 10.1182/bloodadvances.2024013540

  View details for PubMedID 39042903

• CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study. Lancet (London, England) Frank, M. J., Baird, J. H., Kramer, A. M., Srinagesh, H. K., Patel, S., Brown, A. K., Oak, J. S., Younes, S. F., Natkunam, Y., Hamilton, M. P., Su, Y. J., Agarwal, N., Chinnasamy, H., Egeler, E., Mavroukakis, S., Feldman, S. A., Sahaf, B., Mackall, C. L., Muffly, L., Miklos, D. B. 2024

  Abstract

  Outcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR19). CD22 is a nearly universally expressed B-cell surface antigen and the efficacy of a CD22-directed CAR T-cell therapy (CAR22) in large B-cell lymphoma is unknown, which was what we aimed to examine in this study.In this single centre, open-label, dose-escalation phase 1 trial, we intravenously administered CAR22 at two dose levels (1 million and 3 million CAR22-positive T cells per kg of bodyweight) to adult patients (aged ≥18 years) who relapsed after CAR19 or had CD19-negative large B-cell lymphoma. The primary endpoints were manufacturing feasibility, safety measured by the incidence and severity of adverse events and dose-limiting toxicities, and identification of the maximum tolerated dose (ie, the recommended phase 2 dose). This study is registered with ClinicalTrials.gov (NCT04088890) and is active, but closed for enrolment.From Oct 17, 2019, to Oct 19, 2022, a total of 41 patients were assessed for eligibility; however, one patient withdrew. 40 patients underwent leukapheresis and 38 (95%) had CAR T-cell products manufactured successfully. The median age was 65 years (range 25-84), 17 (45%) were women, 32 (84%) had elevated pretreatment lactate dehydrogenase, 11 (29%) had refractory disease to all previous therapies, and patients had received a median of four lines of previous therapy (range 3-8). Of the 38 patients treated, 37 (97%) had relapsed after previous CAR19. The identified maximum tolerated dose was 1 million CAR T cells per kg. Of 29 patients who received the maximum tolerated dose, no patients developed a dose-limiting toxicity or grade 3 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome.This trial identifies CD22 as an immunotherapeutic target in large B-cell lymphoma and demonstrates the durable clinical activity of CAR22 in patients with disease progression after CAR19 therapy. Although these findings are promising, it is essential to recognise that this is a phase 1 dose-finding study. Further investigations are warranted to establish the long-term efficacy and to delineate the patient subgroups that will derive the most benefit from this therapeutic approach.National Cancer Institute, National Institutes of Health, Stanford Cancer Institute, Leukemia & Lymphoma Society, Parker Institute for Cancer Immunotherapy, Lymph & Co, and the European Hematology Association.

  View details for DOI 10.1016/S0140-6736(24)00746-3

  View details for PubMedID 38996463

• A Phase 1 Clinical Trial of NKTR-255 with CD19-22 CAR-T Cell Therapy for Refractory B-cell Acute Lymphoblastic Leukemia. Blood Srinagesh, H. K., Jackson, C., Shiraz, P., Jeyakumar, N., Hamilton, M. P., Egeler, E., Mavroukakis, S., Kuo, A., Cancilla, J., Sahaf, B., Agarwal, N., Kanegai, A. M., Kramer, A. M., Arai, S., Bharadwaj, S., Dahiya, S., Hosoya, H., Johnston, L. J., Kennedy, V. E., Liedtke, M., Lowsky, R., Mikkilineni, L., Negrin, R. S., Rezvani, A. R., Sidana, S., Shizuru, J. A., Smith, M., Weng, W. K., Feldman, S. A., Frank, M. J., Lee, Z., Tagliaferri, M., Marcondes, A. M., Miklos, D. B., Mackall, C. L., Muffly, L. 2024

  Abstract

  While chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies, many patients relapse and therefore strategies to improve antitumor immunity are needed. We previously designed a novel autologous bispecific CAR targeting CD19 and CD22 (CAR19-22), which was well tolerated and associated with high response rates but relapse was common. Interleukin-15 (IL15) induces proliferation of diverse immune cells and can augment lymphocyte trafficking. Here, we report the results of a phase 1 clinical trial of the first combination of a novel recombinant polymer-conjugated IL15 receptor agonist (NKTR-255), with CAR19-22, in adults with relapsed / refractory B-cell acute lymphoblastic leukemia. Eleven patients were enrolled, nine of whom successfully received CAR19-22 followed by NKTR-255. There were no dose limiting toxicities, with transient fever and myelosuppression as the most common possibly related toxicities. We observed favorable efficacy with eight out of nine patients (89%) achieving measurable residual disease negative remission. At 12 months, progression-free survival for NKTR-255 was double that of historical controls (67% vs 38%). We performed correlative analyses to investigate the effects of IL15 receptor agonism. Cytokine profiling showed significant increases in IL15 and the chemokines CXCL9 and CXCL10. The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood and ten-fold increases in CSF CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible and associated with high rates of durable responses (NCT03233854).

  View details for DOI 10.1182/blood.2024024952

  View details for PubMedID 38968138

• Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma. Journal for immunotherapy of cancer Bharadwaj, S., Lau, E., Hamilton, M. P., Goyal, A., Srinagesh, H., Jensen, A., Lee, D., Mallampet, J., Elkordy, S., Syal, S., Patil, S., Latchford, T., Sahaf, B., Arai, S., Johnston, L. J., Lowsky, R., Negrin, R., Rezvani, A. R., Shizuru, J., Meyer, E. H., Shiraz, P., Mikkilineni, L., Weng, W. K., Smith, M., Sidana, S., Muffly, L., Maecker, H. T., Frank, M. J., Mackall, C., Miklos, D., Dahiya, S. 2024; 12 (7)

  Abstract

  Fludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepletion despite a lack of clinical safety and efficacy data. To fill this gap in the literature, we evaluated the safety, efficacy, and expansion kinetics of bendamustine as lymphodepletion prior to axicabtagene ciloleucel (axi-cel) therapy.84 consecutive patients with relapsed or refractory large B-cell lymphoma treated with axi-cel and managed with a uniform toxicity management plan at Stanford University were studied. 27 patients received alternative lymphodepletion with bendamustine while 57 received FC.Best complete response rates were similar (73.7% for FC and 74% for bendamustine, p=0.28) and there was no significant difference in 12-month progression-free survival or overall survival estimates (p=0.17 and p=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was similar in both the cohorts. Bendamustine cohort experienced lower proportions of hematological toxicities and antibiotic use for neutropenic fever. Immune reconstitution, as measured by quantitative assessment of cellular immunity, was better in bendamustine cohort as compared with FC cohort. CAR T expansion as measured by peak expansion and area under the curve for expansion was comparable between cohorts.Bendamustine is a safe and effective alternative lymphodepletion conditioning for axi-cel with lower early hematological toxicity and favorable immune reconstitution.

  View details for DOI 10.1136/jitc-2024-008975

  View details for PubMedID 38955420

• Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel. Journal of hematology & oncology Zanwar, S., Sidana, S., Shune, L., Puglianini, O. C., Pasvolsky, O., Gonzalez, R., Dima, D., Afrough, A., Kaur, G., Davis, J. A., Herr, M., Hashmi, H., Forsberg, P., Sborov, D., Anderson, L. D., McGuirk, J. P., Wagner, C., Lieberman-Cribbin, A., Rossi, A., Freeman, C. L., Locke, F. L., Richard, S., Khouri, J., Lin, Y., Patel, K. K., Kumar, S. K., Hansen, D. K. 2024; 17 (1): 42

  Abstract

  Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively (p<0.001). The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p<0.0001) for the non-EMD cohort. In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.5 (1.1-2.2), p=0.02]. The median overall survival was 14.8 months [95% CI: 9-Not reached (NR)] vs. 26.9 months (26.3 vs. NR, p=0.006) for the EMD and non-EMD cohorts, respectively. Extramedullary disease represents an independent predictor of inferior day 90 ORR and PFS among patients treated with ide-cel.

  View details for DOI 10.1186/s13045-024-01555-4

  View details for PubMedID 38845015

• Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The U.S. Myeloma Immunotherapy Consortium Real World Experience. Transplantation and cellular therapy Khouri, J., Dima, D., Li, H., Hansen, D., Sidana, S., Shune, L., Anwer, F., Sborov, D., Wagner, C., Kocoglu, M. H., Atrash, S., Voorhees, P., Peres, L., Hovanky, V., Simmons, G., Williams, L., Raza, S., Afrough, A., Anderson, L., Fererri, C., Hashmi, H., Davis, J., McGuirk, J., Goldsmith, S., Borogovac, A., Lin, Y., Midha, S., Nadeem, O., Locke, F. L., Baz, R., Hamilton, B., Alsina, M., Sauter, C., Patel, K., Kaur, G. 2024

  Abstract

  Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed-refractory multiple myeloma (RRMM). The aim of this study was to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel.Data were retrospectively collected from 11 institutions in the U.S. Impact of ALC parameters including pre-apheresis (pre-A), pre-lymphodepletion (pre-LD), absolute and percent difference from pre-A to pre-LD on clinical outcomes after ide-cel were examined using survival analysis. A new ALC profile was created based on univariate analysis and included three groups: Normal (≥1 × 109/L) pre-LD ALC (LDN), low (<1 × 109/L) pre-LD ALC (LDL) + percent reduction <37.5 (%RL), and LDL ALC + percent reduction ≥37.5 (%RH).214 SOC ide-cel recipients were included in this analysis, median age (IQR) was 64 (57-69) years, median number of prior therapies was 6 (5-9), and median (IQR) follow up time was 5.4 (2.1-8.3) months. Most patients had both low pre-A (75.3%) and pre-LD (77.2%) ALC, and the reduction from pre-A to pre-LD (median 0.65 to 0.55 × 109/L) was statistically significant. Univariate analysis showed that the LDL + %RH group had significantly worse progression-free survival (PFS) and overall survival (OS) compared to the LDL + %RL and LDN ALC groups (6-month PFS: 40% vs 67.6% and 60.9%; 6-month OS: 69.5% vs 87% and 94.3%). In multivariable analysis, after adjusting for age, performance status, cytogenetic risk, use of bridging therapy, and extramedullary disease, PFS did not maintain its statistical significance. However, OS remained significantly worse for LDL + %RH group compared to the LDN ALC group (HR, 95% CI: 4.3, 1.1-17), but the difference between the LDL + %RH vs %RL groups was not statistically significant (HR, 95% CI: 1.7, 0.8-4.0).Our findings indicate that low pre-LD ALC with high percent reduction from pre-A to pre-LD was associated with inferior survival outcomes, particularly OS, in patients who received SOC ide-cel.

  View details for DOI 10.1016/j.jtct.2024.05.025

  View details for PubMedID 38834151

• Ciltacabtagene autoleucel vs standard of care in patients with functional high-risk multiple myeloma: CARTITUDE-4 subgroup analysis. Costa, L. J., Weisel, K. C., van de Donk, N. J., Sidana, S., Cohen, Y. C., Purtill, D., Touzeau, C., de larrea, C., Martinez-Lopez, J., Lendvai, N., Slaughter, A., Lonardi, C., Zhao, M., Li, K., Vogel, M., Koneru, M., Patel, N., Florendo, E., Costa Filho, O., Mateos, M. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557401733

• Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma Garfall, A. L., Nooka, A. K., van de Donk, N. J., Moreau, P., Bhutani, M., Oriol, A., Martin, T. G., Rosinol, L., Mateos, M., Bahlis, N. J., Popat, R., Besemer, B., Martinez-Lopez, J., Krishnan, A. Y., Delforge, M., Huang, L., Vishwamitra, D., Stephenson, T., Chastain, K., Sidana, S. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557401764

• Consensus guidelines and recommendations for the management and response assessment of chimeric antigen receptor T-cell therapy in clinical practice for relapsed and refractory multiple myeloma: a report from the International Myeloma Working Group Immunotherapy Committee. The Lancet. Oncology Lin, Y., Qiu, L., Usmani, S., Joo, C. W., Costa, L., Derman, B., Du, J., Einsele, H., Fernandez de Larrea, C., Hajek, R., Ho, P. J., Kastritis, E., Martinez-Lopez, J., Mateos, M. V., Mikhael, J., Moreau, P., Nagarajan, C., Nooka, A., O'Dwyer, M., Schjesvold, F., Sidana, S., van de Donk, N. W., Weisel, K., Zweegman, S., Raje, N., Otero, P. R., Anderson, L. D., Kumar, S., Martin, T. 2024

  Abstract

  Chimeric antigen receptor (CAR) T-cell therapy has shown promise in patients with late-line refractory multiple myeloma, with response rates ranging from 73 to 98%. To date, three products have been approved: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which are approved by the US Food and Drug Administration, the European Medicines Agency, Health Canada (ide-cel only), and Brazil ANVISA (cilta-cel only); and equecabtagene autoleucel (eque-cel), which was approved by the Chinese National Medical Products Administration. CAR T-cell therapy is different from previous anti-myeloma therapeutics with unique toxic effects that require distinct mitigation strategies. Thus, a panel of experts from the International Myeloma Working Group was assembled to provide guidance for clinical use of CAR T-cell therapy in myeloma. This consensus opinion is from experts in the field of haematopoietic cell transplantation, cell therapy, and multiple myeloma therapeutics.

  View details for DOI 10.1016/S1470-2045(24)00094-9

  View details for PubMedID 38821074

• Real-world impact of bridging therapy on outcomes of ide-cel for myeloma in the U.S. Myeloma Immunotherapy Consortium. Blood cancer journal Afrough, A., Hashmi, H., Hansen, D. K., Sidana, S., Ahn, C., Peres, L. C., Dima, D., Freeman, C. L., Puglianini, O. C., Kocoglu, M. H., Atrash, S., Voorhees, P. M., Shune, L., McGuirk, J. P., Simmons, G., Sborov, D. W., Davis, J. A., Kaur, G., Sannareddy, A., Ferreri, C. J., Gaballa, M. R., Goldsmith, S., Nadeem, O., Midha, S., Wagner, C. B., Locke, F. L., Patel, K. K., Khouri, J., Anderson, L. D., Lin, Y. 2024; 14 (1): 63

  View details for DOI 10.1038/s41408-024-00993-0

  View details for PubMedID 38609386

  View details for PubMedCentralID 5718945

• CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific expansion and toxicity. Blood advances Hamilton, M. P., Craig, E., Gentille Sanchez, C., Mina, A., Tamaresis, J., Kirmani, N., Ehlinger, Z., Syal, S., Good, Z., Sworder, B., Schroers-Martin, J., Lu, Y., Muffly, L., Negrin, R. S., Arai, S., Lowsky, R., Meyer, E., Rezvani, A. R., Shizuru, J. A., Weng, W. K., Shiraz, P., Sidana, S., Bharadwaj, S., Smith, M., Dahiya, S., Sahaf, B., Kurtz, D. M., Mackall, C. L., Tibshirani, R., Alizadeh, A. A., Frank, M. J., Miklos, D. B. 2024

  Abstract

  Chimeric antigen receptor (CAR) T cells directed against CD19 (CAR19) are a revolutionary treatment for B-cell lymphomas. CAR19 cell expansion is necessary for CAR19 function but is also associated with toxicity. To define the impact of CAR19 expansion on patient outcomes, we prospectively followed a cohort of 236 patients treated with CAR19 (brexucabtagene autoleucel or axicabtagene ciloleucel) for mantle cell (MCL), follicular (FL), and large B-cell lymphoma (LBCL) over the course of five years and obtained CAR19 expansion data using peripheral blood immunophenotyping for 188 of these patients. CAR19 expansion was higher in patients with MCL compared to other lymphoma histologic subtypes. Notably, patients with MCL had increased toxicity and required four-fold higher cumulative steroid doses than patients with LBCL. CAR19 expansion was associated with the development of cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and the requirement for granulocyte colony stimulating factor (GCSF) after day 14 post-infusion. Younger patients and those with elevated lactate dehydrogenase (LDH) had significantly higher CAR19 expansion. In general, no association between CAR19 expansion and LBCL treatment response was observed. However, when controlling for tumor burden, we found that lower CAR19 expansion in conjunction with low LDH was associated with improved outcomes in LBCL. In sum, this study finds CAR19 expansion principally associates with CAR-related toxicity. Additionally, CAR19 expansion as measured by peripheral blood immunophenotyping may be dispensable to favorable outcomes in LBCL.

  View details for DOI 10.1182/bloodadvances.2024012637

  View details for PubMedID 38498731

• CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results. Leukemia Schultz, L. M., Jeyakumar, N., Kramer, A. M., Sahaf, B., Srinagesh, H., Shiraz, P., Agarwal, N., Hamilton, M., Erickson, C., Jacobs, A., Moon, J., Baggott, C., Arai, S., Bharadwaj, S., Johnston, L. J., Liedtke, M., Lowsky, R., Meyer, E., Negrin, R., Rezvani, A., Shizuru, J., Sidana, S., Egeler, E., Mavroukakis, S., Tunuguntla, R., Gkitsas-Long, N., Retherford, A., Brown, A. K., Gramstrap-Petersen, A. L., Ibañez, R. M., Feldman, S. A., Miklos, D. B., Mackall, C. L., Davis, K. L., Frank, M., Ramakrishna, S., Muffly, L. 2024

  Abstract

  Chimeric antigen receptor (CAR) T cells targeting CD22 (CD22-CAR) provide a therapeutic option for patients with CD22+ malignancies with progression after CD19-directed therapies. Using on-site, automated, closed-loop manufacturing, we conducted parallel Phase 1b clinical trials investigating a humanized CD22-CAR with 41BB costimulatory domain in children and adults with heavily treated, relapsed/refractory (r/r) B-ALL. Of 19 patients enrolled, 18 had successful CD22-CAR manufacturing, and 16 patients were infused. High grade (3-4) cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS) each occurred in only one patient; however, three patients experienced immune-effector-cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Twelve of 16 patients (75%) achieved CR with an overall 56% MRD-negative CR rate. Duration of response was overall limited (median 77 days), and CD22 expression was downregulated in 4/12 (33%) available samples at relapse. In summary, we demonstrate that closed-loop manufacturing of CD22-CAR T cells is feasible and is associated with a favorable safety profile and high CR rates in pediatric and adult r/r B-ALL, a cohort with limited CD22-CAR reporting.

  View details for DOI 10.1038/s41375-024-02220-y

  View details for PubMedID 38491306

  View details for PubMedCentralID 4993814

• Single Center Randomized Trial of T-reg graft alone versus T-reg graft Plus Tacrolimus for the Prevention of Acute GVHD. Blood advances Bader, C. S., Pavlova, A., Lowsky, R., Muffly, L., Shiraz, P., Arai, S., Johnston, L. J., Rezvani, A. R., Weng, W. K., Miklos, D. B., Frank, M. J., Tamaresis, J. S., Agrawal, V., Bharadwaj, S., Sidana, S., Shizuru, J. A., Fernhoff, N. B., Putnam, A., Killian, S., Xie, B. J., Negrin, R. S., Meyer, E. 2023

  Abstract

  Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies for which graft-versus-host disease (GVHD) remains a major complication. The use of donor T regulatory cells (Tregs) to prevent GVHD appears promising, including in our previous evaluation of an engineered graft product (T-reg graft) consisting of the timed, sequential infusion of CD34+ hematopoietic stem cells and high-purity Tregs followed by conventional T cells. However, whether immunosuppressive prophylaxis can be removed from this protocol remains unclear. We report the results of the first stage of an open-label single-center phase 2 study (NCT01660607) investigating T-reg graft in myeloablative HCT of HLA-matched and 9/10 matched recipients. Twenty-four patients were randomized to receive T-reg graft alone (n=12) or T-reg graft plus single-agent GVHD prophylaxis (n=12) to determine if T-reg graft alone was non-inferior in preventing acute GVHD. All patients developed full donor myeloid chimerism. Patients with T-reg graft alone versus with prophylaxis had an incidence of grade II-IV acute GVHD of 58% versus 8% (p=0.005) and grade III-IV of 17% versus 0% (p=0.149), respectively. The incidence of moderate to severe chronic GVHD was 28% in the T-reg graft alone arm versus 0% with prophylaxis (p=0.056). Among patients with T-reg graft and prophylaxis, CD4+ T cell:Treg ratios were reduced after transplantation, gene-expression profiles showed reduced CD4+ proliferation, and the achievement of full donor T cell chimerism was delayed. This study indicates that T-reg graft with single-agent tacrolimus is preferred to T-reg graft alone for the prevention of acute GVHD. Clinical Trial #: NCT01660607.

  View details for DOI 10.1182/bloodadvances.2023011625

  View details for PubMedID 38091578

• Managing side effects: guidance for use of immunotherapies in multiple myeloma. Hematology. American Society of Hematology. Education Program Liang, E. C., Sidana, S. 2023; 2023 (1): 348-356

  Abstract

  Chimeric antigen receptor T-cell therapy and bispecific T-cell recruiting antibodies have transformed the treatment landscape for relapsed/refractory multiple myeloma, with B-cell maturation antigen being the most common target and other targets in clinical development. However, these therapies are associated with unique and severe toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), delayed neurotoxicity, cytopenias, and infection. In addition, immune effector cell-associated hemophagocytic lymphohistiocytosis (HLH)-like syndrome (IEC-HS), which exhibits overlap between CRS and HLH, can be challenging to diagnose and treat. In this review, we provide an overview of toxicities associated with novel immunotherapies for treatment of multiple myeloma and describe management recommendations. The pathophysiology and risk factors behind these toxicities are not yet comprehensively understood. Based on consensus recommendations, treatment for CRS consists of tocilizumab and steroids, while treatment for ICANS includes steroids and anakinra in severe cases. Management of cytopenias and infection is similar to post-hematopoietic cell transplantation principles with antimicrobial prophylaxis, growth factor support, immunoglobulin replacement, and vaccinations. In contrast, effective treatments for delayed neurotoxicity and IEC-HS are lacking, although steroids and anakinra are commonly used. Management of all these toxicities should include a broad differential and multidisciplinary collaboration with infectious diseases, neurology, and/or critical care providers.

  View details for DOI 10.1182/hematology.2023000435

  View details for PubMedID 38066898

• Integrating Immune Therapies for the Treatment of Multiple Myeloma. Journal of the National Comprehensive Cancer Network : JNCCN Mikkilineni, L., Sidana, S. 2023; 21 (12): 1303-1311

  Abstract

  Patients with relapsed or refractory multiple myeloma (RRMM) that is refractory to a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38 antibody (triple-class refractory MM) have poor outcomes. Recently, 2 classes of T-cell engaging therapies-CAR T-cell therapy and bispecific T-cell engaging antibodies (BsAbs)-have resulted in unprecedented response rates and survival outcomes in these heavily pretreated patients. The most common targets are BCMA and GPRC5D, with other targets in development. The main classes of adverse effects include cytokine release syndrome, neurotoxicity, infections, and cytopenias, as well as adverse effects unique to specific products. As of September 2023, 2 BCMA-targeting CAR-T cell products, 2 BCMA-targeting BsAbs, and 1 GPRC5D-targeting BsAb, are FDA-approved for standard-of-care use in patients with RRMM who received at least 4 prior lines of therapy, including prior treatment with a proteasome inhibitor, an IMiD, and an anti-CD38 antibody. Earlier-line use is under investigation and has shown promising results. Several other investigational CAR-T constructs and bispecific antibodies are in clinical development. As these therapies become more widely used, including in earlier-line setting, efforts to understand optimal sequencing and mitigate toxicities remain critical.

  View details for DOI 10.6004/jnccn.2023.7100

  View details for PubMedID 38081142

• CAR19 Therapy Drives Expansion of Clonal Hematopoiesis and Associated Cytopenias Hamilton, M. P., Sworder, B. J., Alig, S. K., Good, Z., Boegeholz, J., Schroers-Martin, J., Tamaresis, J., Esfahani, M., Lu, Y., Olsen, M., Liu, C., Ehlinger, Z., Desai, M., Liu-Fei, F., Muffly, L. S., Negrin, R. S., Arai, S., Johnston, L., Lowsky, R., Meyer, E. H., Rezvani, A. R., Shizuru, J., Weng, W., Shiraz, P., Sidana, S., Bharadwaj, S., Smith, M., Dahiya, S., Sahaf, B., Diehn, M., Frank, M. J., Mackall, C. L., Kurtz, D. M., Miklos, D. B., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-182522

  View details for Web of Science ID 001159306701117

• Alternative Lymphodepletion Strategies Lead to Similar Response Rates and Toxicities in Standard-of-Care BCMA-Directed CAR-T Therapy in Relapsed Refractory Multiple Myeloma Midha, S., Gurumurthi, A., Costello, P., Redd, R. A., Freeman, C. L., Castaneda, O., Gonzalez, R., Ionescu, F., Gaballa, M., Kalariya, N., Khouri, J., Dima, D., Kocoglu, M. H., Sborov, D., Wagner, C. B., Atrash, S., Voorhees, P. M., Hashmi, H., Davis, J. A., Forsberg, P. A., McGuirk, J. P., Shune, L., Herr, M., Reshef, R., Lin, Y., Htut, M., Martin, T., Sidana, S., Hansen, D. K., Nadeem, O., Patel, K. K. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-187565

  View details for Web of Science ID 001159740304110

• Fludarabine Lymphodepletion Exposure Is Associated with Idecabtagene Vicleucel Toxicity in Relapsed and Refractory Multiple Myeloma Patients: Real-World Experience from the US Myeloma Immunotherapy Consortium Wagner, C. B., Sweiss, K., Anto, E., Gonzalez, R., Puglianini, O., Freeman, C. L., Ionescu, F., Patel, K. K., Ferreri, C., Gaballa, M., Shune, L., McGuirk, J. P., Sidana, S., Hovanky, V., Khouri, J., Dima, D., Hashmi, H., Davis, J. A., Afrough, A., Kaur, G., Larry, A. D., Forsberg, P. A., Herr, M., Hansen, D. K., Sborov, D., Kocoglu, M. H. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-187440

  View details for Web of Science ID 001159900800081

• Real World Outcomes with Idecabtagene Vicleucel ( Ide-Cel) CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma Sidana, S., Ahmed, N., Akhtar, O. S., Heim, M., Brazauskas, R., Hansen, D. K., Ferreri, C., Freeman, C. L., Afrough, A., Anderson, L. D., Dhakal, B., Dhanda, D., Gowda, L., Hashmi, H., Harrison, M., Kitali, A., Mirza, S., Patel, J., Patwardhan, P., Usmani, S. Z., Patel, K. K., Ganguly, S., Pasquini, M. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-181762

  View details for Web of Science ID 001159306704051

• Clinical Experience with Cranial Nerve Impairment in the CARTITUDE-1, CARTITUDE-2 Cohorts A, B, and C, and Cartitude-4 Studies of Ciltacabtagene Autoleucel (Cilta-cel) Van De Donk, N. J., Sidana, S., Schecter, J. M., Jackson, C., Lendvai, N., De Braganca, K. C., Slaughter, A., Lonardi, C., Vlummens, P., Varsos, H., Corsale, C., Madduri, D., Jadidi, S., Gu, J., Zhao, H., Li, K., Lee, E., Marquez, L., Zhao, M., Yeh, T., Chen, D., Florendo, E., Patel, N., Akram, M., Perez-Larraya, J., Rodriguez Otero, P. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-178743

  View details for Web of Science ID 001159740304112

• Phase 1 Trial Results for Patients with Advanced Hematologic Malignancies Undergoing Reduced Intensity Allogeneic HCT with Orca-T Donor Cell Therapy Product and Single Agent Tacrolimus Villar-Prados, A., Meyer, E. H., Sutherland, K., Negrin, R. S., Arai, S., Frank, M. J., Johnston, L., Lowsky, R., Miklos, D. B., Muffly, L. S., Dahiya, S., Rezvani, A. R., Sidana, S., Shiraz, P., Shizuru, J., Weng, W., Smith, M., Bharadwaj, S., Tamaresis, J., Pavlova, A., McClellan, S. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-188162

  View details for Web of Science ID 001159740304171

• CAR T-Cell therapy for Myeloma: Where are we now and what is needed to move CAR T-cells forward to earlier lines of therapy? Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Transplantation and cellular therapy Anderson, L. D., Dhakal, B., Jain, T., Oluwole, O. O., Shah, G. L., Sidana, S., Perales, M. A., Pasquini, M. C. 2023

  Abstract

  Since 2021, two B-Cell Maturation Antigen (BCMA) directed chimeric antigen receptor T-cell (CAR T-cell) therapies, Idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel), have been approved by the US FDA for relapsed or refractory multiple myeloma (RRMM) after four or more prior lines of therapy including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody. The two products have both shown unprecedented activity in RRMM, but relapses are still common, and access and safety of CAR T-cells in patients with rapidly progressing advanced disease is not ideal. Sequencing CAR T-cell therapy with other options, including the 2 recently approved BCMA directed T-cell engaging bispecific antibodies (TCE BsAbs) teclistamab and elranatamab, has become increasingly challenging due to data showing inferior outcomes from CAR T-cells after prior BCMA directed therapy. This has led to the consideration of using CAR T-cell therapy earlier in the course of disease for myeloma, when T-cells are potentially healthier and the myeloma is less aggressive. To address the question of earlier use of CAR T Cells, several trials are either ongoing or planned, and results have recently been reported for 2 randomized trials of CAR T-cells showing improved progression free survival compared to standard of care therapy in 2nd line (CARTITUDE-4) or 3rd line therapy (KarMMA-3). With the anticipation of the FDA possibly expanding approval of CAR T cells to earlier lines of myeloma therapy, the American Society for Transplantation and Cellular Therapy (ASTCT) convened a group of experts to provide a comprehensive review of the studies that led to approval of CAR T-cells in late line therapy of myeloma, discuss the recently reported and ongoing studies designed to move CAR T-cell therapy to earlier lines of therapy, and to share insights and considerations for sequencing therapy and optimization of patient selection for BCMA directed therapies in current practice.

  View details for DOI 10.1016/j.jtct.2023.10.022

  View details for PubMedID 37913909

• Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma: U.S. Myeloma Immunotherapy Consortium real world experience. Haematologica Hashmi, H., Hansen, D. K., Peres, L. C., Puglianini, O. C., Freeman, C., De Avila, G., Sidana, S., Shune, L., Sborov, D. W., Davis, J., Wagner, C., Kocoglu, M. H., Atrash, S., Voorhees, P., Simmons, G., Ferreri, C., Kalariya, N., Anderson, L. D., Afrough, A., Dima, D., Khouri, J., McGuirk, J., Locke, F., Baz, R., Patel, K. K., Alsina, M. 2023

  Abstract

  While response rates and survival outcomes have been very promising for idecabtagene vicleucel (ide-cel), a proportion of patients do not respond or relapse early after this B-cell maturation antigen (BCMA) targeted CAR T-cell therapy. Understanding the characteristics of these patients is important for patient selection and development of novel strategies to improve outcomes. We evaluated factors associated with early progression (progression or death due to myeloma ≤ 3 months after CAR T infusion) in patients treated with standard of care ide-cel at 11 US academic centers. Among 211 patients that received ide-cel, 43 patients had a progressive event ≤ 3 months of infusion. Patients with a history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, use of bridging therapy, Hispanic ethnicity, plasma cell leukemia and t(4;14) were more likely to progress ≤ 3 months of infusion (p < 0.05). Of these risk factors for early progression identified in univariate analyses, history of extramedullary disease, prior BCMA targeted therapy, elevated ferritin at lymphodepletion, plasma cell leukemia, and t(4;14) were associated with worse progression-free survival (PFS) in multivariable analysis. Presence of three or more of these factors had a significant negative impact on PFS (p < 0.001; median PFS for ≥ 3 factors, 3.2 months vs. 0 factors, 14.1 months). This study helps identify patients at high risk of early progression after CAR T who may benefit from specific interventions pre and post CAR T to improve outcomes.

  View details for DOI 10.3324/haematol.2023.283888

  View details for PubMedID 37855036

• Racial and ethnic differences in clinical outcomes among multiple myeloma patients treated with CAR T-cell therapy. Blood advances Peres, L. C., Oswald, L. B., Dillard, C. M., De Avila, G., Nishihori, T., Blue, B. J., Freeman, C. L., Locke, F. L., Alsina, M., Castaneda Puglianini, O. A., Shune, L., Sborov, D. W., Wagner, C., Dima, D., Hashmi, H., Davis, J. A., Kocoglu, M. H., Badros, A. Z., Atrash, S., Simmons, G., Kalariya, N., Ferreri, C. J., Anderson, L. D., Afrough, A., Kaur, G., Lin, Y., Liu, L., Nadeem, O., Voorhees, P. M., Khouri, J., McGuirk, J. P., Sidana, S., Hansen, D. K., Patel, K. K. 2023

  Abstract

  Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain FDA approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 RRMM patients (28% racial and ethnic minority patients) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) Non-Hispanic Black, and 149 (72%) Non-Hispanic White RRMM patients. Compared to Hispanic and Non-Hispanic White patients, Non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P=0.02) and baseline ferritin (362.0 vs. 307.0 vs. 680.5, respectively; P=0.08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P=0.04). Although best overall response rate was lower among Hispanic patients (59%) compared to Non-Hispanic Black (86%) and White patients (86%; P=0.01), there were no racial and ethnic differences in progression-free or overall survival. We provide the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all RRMM patients. These findings should be confirmed in larger samples of diverse RRMM patients with longer follow-up time.

  View details for DOI 10.1182/bloodadvances.2023010894

  View details for PubMedID 37855718

• Bendamustine vs. fludarabine/cyclophosphamide lymphodepletion prior to BCMA CAR-T cell therapy in multiple myeloma. Blood cancer journal Sidana, S., Hosoya, H., Jensen, A., Liu, L., Goyal, A., Hovanky, V., Sahaf, B., Bharadwaj, S., Latchford, T., Arai, S., Leahy, S., Mei, M., Budde, L. E., Muffly, L. S., Frank, M. J., Dahiya, S., Htut, M., Miklos, D., Janakiram, M. 2023; 13 (1): 158

  View details for DOI 10.1038/s41408-023-00929-0

  View details for PubMedID 37833271

  View details for PubMedCentralID PMC10576036

• First phase 3 results from CARTITUDE-4: cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma Dhakal, B., Yong, K., Harrison, S., Mateos, M., Moreau, P., van de Donk, N. W., Sidana, S., Popat, R., Lendvai, N., Lonardi, C., Slaughter, A., Schecter, J. M., Li, K., Zudaire, E., Chen, D., Gilbert, J., Yeh, T., Pacaud, L., Patel, N., San-Miguel, J., Einsele, H. KARGER. 2023: 81-82

  View details for Web of Science ID 001091456900164

• Long-term follow-up from MajesTEC-1 of Teclistamab, a B-cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in patients with Relapsed/Refractory Multiple Myeloma (RRMM) Donk, V. W., Moreau, P., Garfall, A. L., Bhutani, M., Oriol, A., Nooka, A. K., Martin, T. G., Rosinol, L., Mateos, M., Bahlis, N., Popat, R., Besemer, B., Lopez, M. J., Krishnan, A., Delforge, M., Trancucci, D., Verona, R., Stephenson, T., Chastain, K., Sidana, S. KARGER. 2023: 124

  View details for Web of Science ID 001091456900265

• Long-Term Follow-Up From the MajesTEC-1 Study of Teclistamab, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Patients With Relapsed/Refractory Multiple Myeloma (RRMM) van de Donk, N. J., Moreau, P., Garfall, A. L., Bhutani, M., Oriol, A., Nooka, A. K., Martin, T. G., Rosinol, L., Mateos, M., Bahlis, N., Popat, R., Besemer, B., Martinez Lopez, J., Krishnan, A., Delforge, M., Trancucci, D., Verona, R. I., Stephenson, T., Chastain, K., Sidana, S. WILEY. 2023: S25-S26

  View details for Web of Science ID 001098086400041

• Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment. Haematologica Sidana, S., Peres, L. C., Hashmi, H., Hosoya, H., Ferreri, C., Khouri, J., Dima, D., Atrash, S., Voorhees, P., Simmons, G., Sborov, D. W., Kalariya, N., Hovanky, V., Bharadwaj, S., Miklos, D., Wagner, C., Kocoglu, M. H., Kaur, G., Davis, J. A., Midha, S., Janakiram, M., Freeman, C., Alsina, M., Locke, F., Gonzalez, R., Lin, Y., McGuirk, J., Afrough, A., Shune, L., Patel, K. K., Hansen, D. K. 2023

  Abstract

  We evaluated patients with relapsed multiple myeloma with renal impairment (RI treated with standard of care ide-cel, as outcomes with CAR-T therapy are unknown in this population. RI was defined as creatinine clearance (CrCl < 50 ml/min. CrCl of < 30 ml/min or dialysis dependence were defined as severe RI. The study cohort included 214 patients, 28 (13% patients with RI, including 11 patients severe RI (dialysis, n=1. Patients with RI were older, more likely to be female and had higher likelihood of having R-ISS stage 3 disease. Rates and severity of CRS (89% vs 84%, grade ≥ 3: 7% vs 2% and ICANS (23% vs 20% were similar in patients with and without RI, respectively. Patients with RI had higher incidence of short-term ≥ grade 3 cytopenias, although cytopenias were similar by 3 months following CAR-T. Renal function did not worsen after CAR-T in patients with RI. Response rates (93% vs 82% and survival outcomes (median PFS: 9 vs 8 months, p=0.26 were comparable in patients with and without RI, respectively. Treatment with ide-cel is feasible in patients with RI, with a comparable safety and efficacy profile as patients without RI, with notable exception of higher short-term high-grade cytopenias.

  View details for DOI 10.3324/haematol.2023.283940

  View details for PubMedID 37731379

• Impact of bridging therapy (BT) on outcome of relapsed refractory multiple myeloma (RRMM) with Ide-cel CAR T-cell therapy: real-world experience from the US myeloma CAR T consortium Afrough, A., Hashmi, H., Hansen, D., Sidana, S., Ahn, C., Dima, D., Freeman, C., Puglianini, O., Kocoglu, M., Atrash, S., Voorhees, P., Shune, L., Simmons, G., Sborov, D., Ferreri, C., Wagner, C., Patel, K., Khouri, J., Anderson, L., Lin, Y. CIG MEDIA GROUP, LP. 2023: S33

  View details for Web of Science ID 001079705400054

• Long-Term Follow-Up From MajesTEC-1 of Teclistamab, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Patients With Relapsed/Refractory Multiple Myeloma (RRMM) van de Donk, N., Moreau, P., Garfall, A., Bhutani, M., Oriol, A., Nooka, A., Martin, T., Rosinol, L., Mateos, M., Bahlis, N., Popat, R., Besemer, B., Martinez Lopez, J., Krishnan, A., Delforge, M., Trancucci, D., Verona, R., Stephenson, T., Chastain, K., Sidana, S. CIG MEDIA GROUP, LP. 2023: S477-S478

  View details for Web of Science ID 001062479600544

• Safety and efficacy of standard of care ciltacabtagene autoleucel (Cilta-cel) for relapsed/refractory multiple myeloma (RRMM): real world experience Sidana, S., Patel, K., Peres, L., Bansal, R., Kocoglu, M., Shune, L., Atrash, S., Smith, K., Ferreri, C., Dhakal, B., Chhabra, S., Parrondo, R., Costello, P., Midha, S., Martin, T., Simmons, G., Alsina, M., Htut, M., Voorhees, P., Sborov, D., Khouri, J., Wong, S., Janakiram, M., Lin, Y., Hansen, D. CIG MEDIA GROUP, LP. 2023: S61-S62

  View details for Web of Science ID 001079705400101

• Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy. Blood cancer journal Ferreri, C. J., Hildebrandt, M. A., Hashmi, H., Shune, L. O., McGuirk, J. P., Sborov, D. W., Wagner, C. B., Kocoglu, M. H., Rapoport, A., Atrash, S., Voorhees, P. M., Khouri, J., Dima, D., Afrough, A., Kaur, G., Anderson, L. D., Simmons, G., Davis, J. A., Kalariya, N., Peres, L. C., Lin, Y., Janakiram, M., Nadeem, O., Alsina, M., Locke, F. L., Sidana, S., Hansen, D. K., Patel, K. K., Castaneda Puglianini, O. A. 2023; 13 (1): 117

  Abstract

  Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT.

  View details for DOI 10.1038/s41408-023-00886-8

  View details for PubMedID 37558706

  View details for PubMedCentralID 9713049

• First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. Yong, K., Harrison, S. J., Mateos, M., Moreau, P., van de Donk, N. J., Sidana, S., Popat, R., Lendvai, N., Lonardi, C., Slaughter, A., Schecter, J., Li, K., Zudaire, E., Chen, Y., Gilbert, J., Bubuteishvili-Pacaud, L., Patel, N., San-Miguel, J., Einsele, H. LIPPINCOTT WILLIAMS & WILKINS. 2023: LBA106

  View details for DOI 10.1200/JCO.2023.41.17_suppl.LBA106

  View details for Web of Science ID 001182783300013

• First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. Dhakal, B., Yong, K., Harrison, S. J., Mateos, M., Moreau, P., van de Donk, N. J., Sidana, S., Popat, R., Lendvai, N., Lonardi, C., Slaughter, A., Schecter, J., Li, K., Zudaire, E., Chen, Y., Gilbert, J., Bubuteishvili-Pacaud, L., Patel, N., San-Miguel, J., Einsele, H. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001043181100008

• Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. The New England journal of medicine San-Miguel, J., Dhakal, B., Yong, K., Spencer, A., Anguille, S., Mateos, M. V., Fernández de Larrea, C., Martínez-López, J., Moreau, P., Touzeau, C., Leleu, X., Avivi, I., Cavo, M., Ishida, T., Kim, S. J., Roeloffzen, W., van de Donk, N. W., Dytfeld, D., Sidana, S., Costa, L. J., Oriol, A., Popat, R., Khan, A. M., Cohen, Y. C., Ho, P. J., Griffin, J., Lendvai, N., Lonardi, C., Slaughter, A., Schecter, J. M., Jackson, C. C., Connors, K., Li, K., Zudaire, E., Chen, D., Gilbert, J., Yeh, T. M., Nagle, S., Florendo, E., Pacaud, L., Patel, N., Harrison, S. J., Einsele, H. 2023

  Abstract

  Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR-T cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival.A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%).A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).

  View details for DOI 10.1056/NEJMoa2303379

  View details for PubMedID 37272512

• Safety and efficacy of standard of care (SOC) ciltacabtagene autoleucel (Cilta-cel) for relapsed/refractory multiple myeloma (RRMM). Hansen, D. K., Patel, K. K., Peres, L. C., Kocoglu, M. H., Shune, L., Simmons, G., Ferreri, C. J., Atrash, S., Parrondo, R., Chhabra, S., Costello, P., Midha, S., Alsina, M., Voorhees, P. M., Htut, M., Sborov, D. W., Khouri, J., Janakiram, M., Lin, Y., Sidana, S. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772003530

• Embracing Myeloma Chimeric Antigen Receptor-T: From Scientific Design to Clinical Impact. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting Hosoya, H., Rodriguez-Otero, P., Sidana, S., Borrello, I. M. 2023; 43: e389860

  Abstract

  Despite recent advancement of treatment strategies in multiple myeloma (MM), patients with relapsed/refractory MM disease, particularly after triple-class refractoriness, continue to have poor prognosis. Chimeric antigen receptor (CAR-T) cells were developed and applied to improve outcomes in this setting, and two products, idecabtagene vicleucel and ciltacabtagene autoleucel, both targeting B-cell maturation antigen, have been approved by the Food and Drug Administration in the United States and European Medicines Agency in Europe. Both have shown unprecedented clinical outcomes with high response rate and prolonged progression-free survival and overall survival in this patient population with grim prognosis. Currently, further investigations are ongoing for CAR-T targeting different tumor antigens such as G protein-coupled receptor, class C, group 5, member D or with different combinations of intracellular signaling domains, as well as fourth-generation CAR-T with antigen-unrestricted inducible cytokines. Although CAR-T therapies hold hopes and enthusiasm from the myeloma community, several hurdles remain before these treatments become available for all patients in need. These barriers include CAR-T-cell manufacturing availability, access to administering centers, financial cost, caregivers' availability, and socioeconomic and racial disparities. Expanding clinical trial eligibility criteria and real-world data collection and analysis is crucial to understand the efficacy and safety of CAR-T in the patient cohort who tends to be excluded from current trials.

  View details for DOI 10.1200/EDBK_389860

  View details for PubMedID 37290016

• Long-term follow-up from MajesTEC-1 of teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). van de Donk, N. J., Moreau, P., Garfall, A. L., Bhutani, M., Oriol, A., Nooka, A. K., Martin, T. G., Rosinol, L., Mateos, M., Bahlis, N. J., Popat, R., Besemer, B., Martinez-Lopez, J., Krishnan, A. Y., Delforge, M., Trancucci, D., Verona, R., Stephenson, T., Chastain, K., Sidana, S. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772003529

• Impact of bridging therapy (BT) on outcome of relapsed refractory multiple myeloma (RRMM) with Ide-cel CAR T-cell therapy: Real-world experience from the US myeloma CAR T consortium. Afrough, A., Hashmi, H., Hansen, D. K., Sidana, S., Ahn, C., Dima, D., Freeman, C. L., Puglianini, O., Kocoglu, M. H., Atrash, S., Voorhees, P. M., Shune, L., Simmons, G., Sborov, D. W., Ferreri, C. J., Wagner, C., Patel, K. K., Khouri, J., Anderson, L. D., Lin, Y. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772003531

• Reply to R. Chakraborty et al. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Hansen, D. K., Sidana, S., Peres, L. C., Patel, K. K. 2023: JCO2300568

  View details for DOI 10.1200/JCO.23.00568

  View details for PubMedID 37235841

• Plain language summary of the MajesTEC-1 study of teclistamab for the treatment of people with relapsed or refractory multiple myeloma. Future oncology (London, England) Moreau, P., van de Donk, N. W., Nahi, H., Oriol, A., Nooka, A. K., Martin, T., Rosinol, L., Karlin, L., Benboubker, L., Mateos, M., Popat, R., Martinez-Lopez, J., Sidana, S., Delforge, M., Pei, L., Trancucci, D., Olyslager, Y., Uhlar, C., Stephenson, T., Rampelbergh, R. V., Banerjee, A., Kobos, R., Usmani, S. Z. 2023

  Abstract

  WHAT IS THIS SUMMARY ABOUT?: This is a summary of a phase 1-2 clinical trial called MajesTEC-1. This trial tested the cancer drug teclistamab in people with relapsed or refractory multiple myeloma, a cancer that forms in a certain type of white blood cells known as plasma cells. Most participants who took part in the study had at least 3 prior treatments for multiple myeloma before their cancer came back.HOW WAS THE STUDY IN THIS SUMMARY CONDUCTED?: A total of 165 participants from 9 countries were included in this study. All participants were given teclistamab once per week and monitored for side effects. Once participants started taking teclistamab, they were checked regularly to monitor if their cancer had no change, improved (responded to treatment), or worsened or spread (known as disease progression).WHAT WERE THE RESULTS OF THE STUDY?: After approximately 14.1months of follow-up (from 2020 to 2021), 63% of participants who were given teclistamab had a decrease in myeloma burden, meaning that they responded to treatment with teclistamab. Participants who responded to teclistamab lived without their myeloma coming back for approximately 18.4months. The most common side effects were infections, cytokine release syndrome, abnormally low white and red blood cell counts (neutropenia, lymphopenia, and anemia), and low platelet cell counts (thrombocytopenia). Approximately 65% of participants experienced serious side effects.WHAT DO THE RESULTS OF THIS STUDY MEAN?: Overall, more than half of the participants (63%) in the MajesTEC-1 study responded to treatment with teclistamab despite previous myeloma treatment failures. Clinical Trial Registration: NCT03145181, NCT04557098 (ClinicalTrials.gov).

  View details for DOI 10.2217/fon-2023-0171

  View details for PubMedID 37132225

• Impact of bortezomib-based versus lenalidomide maintenance therapy on outcomes of patients with high-risk multiple myeloma. Cancer Bumma, N., Dhakal, B., Fraser, R., Estrada-Merly, N., Anderson, K., Freytes, C. O., Hildebrandt, G. C., Holmberg, L., Krem, M. M., Lee, C., Lekakis, L., Lazarus, H. M., Mian, H., Murthy, H. S., Nathan, S., Nishihori, T., Parrondo, R., Patel, S. S., Solh, M., Strouse, C., Vesole, D. H., Kumar, S., Qazilbash, M. H., Shah, N., D'Souza, A., Sidana, S. 2023

  Abstract

  BACKGROUND: Lenalidomide maintenance after autologous stem cell transplant (ASCT) in multiple myeloma (MM) results in superior progression-free survival and overall survival. However, patients with high-risk multiple myeloma (HRMM) do not derive the same survival benefit from lenalidomide maintenance compared with standard-risk patients. The authors sought to determine the outcomes of bortezomib-based maintenance compared with lenalidomide maintenance in patients with HRMM undergoing ASCT.METHODS: In total, the authors identified 503 patients with HRMM who were undergoing ASCT within 12months of diagnosis from January 2013 to December 2018 after receiving triplet novel-agent induction in the Center for International Blood and Marrow Transplant Research database. HRMM was defined as deletion 17p, t(14;16), t(4;14), t(14;20), or chromosome 1q gain.RESULTS: Three hundred fifty-seven patients (67%) received lenalidomide alone, and 146 (33%) received bortezomib-based maintenance (with bortezomib alone in 58%). Patients in the bortezomib-based maintenance group were more likely to harbor two or more high-risk abnormalities and International Staging System stage III disease (30% vs. 22%; p=.01) compared with the lenalidomide group (24% vs. 15%; p<.01). Patients who were receiving lenalidomide maintenance had superior progression-free survival at 2years compared with those who were receiving either bortezomib monotherapy or combination therapy (75% vs. 63%; p=.009). Overall survival at 2years was also superior in the lenalidomide group (93% vs. 84%; p=.001).CONCLUSIONS: No superior outcomes were observed in patients with HRMM who received bortezomib monotherapy or (to a lesser extent) in those who received bortezomib in combination as maintenance compared with lenalidomide alone. Until prospective data from randomized clinical trials are available, post-transplant therapy should be tailored to each patient with consideration for treating patients in clinical trials that target novel therapeutic strategies for HRMM, and lenalidomide should remain a cornerstone of treatment.

  View details for DOI 10.1002/cncr.34778

  View details for PubMedID 37021929

• Publisher Correction: Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results. Nature medicine Mailankody, S., Matous, J. V., Chhabra, S., Liedtke, M., Sidana, S., Oluwole, O. O., Malik, S., Nath, R., Anwer, F., Cruz, J. C., Htut, M., Karski, E. E., Lovelace, W., Dillon, M., Butz, E., Ying, W., Balakumaran, A., Kumar, S. K. 2023

  View details for DOI 10.1038/s41591-023-02306-7

  View details for PubMedID 36932247

• Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results. Nature medicine Mailankody, S., Matous, J. V., Chhabra, S., Liedtke, M., Sidana, S., Oluwole, O. O., Malik, S., Nath, R., Anwer, F., Cruz, J. C., Htut, M., Karski, E. E., Lovelace, W., Dillon, M., Butz, E., Ying, W., Balakumaran, A., Kumar, S. K. 2023

  Abstract

  ALLO-715 is a first-in-class, allogeneic, anti-BCMA CAR T cell therapy engineered to abrogate graft-versus-host disease and minimize CAR T rejection. We evaluated escalating doses of ALLO-715 after lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen in 43 patients with relapsed/refractory multiple myeloma as part A of the ongoing first-in-human phase 1 UNIVERSAL trial. Primary objectives included determination of the safety and tolerability of ALLO-715 and the safety profile of the ALLO-647-containing lymphodepletion regimen. Key secondary endpoints were response rate and duration of response. Grade ≥3 adverse events were reported in 38 (88.0%) of patients. Cytokine release syndrome was observed in 24 patients (55.8%), with 1 grade ≥3 event (2.3%) and neurotoxicity in 6 patients (14%), with no grade ≥3 events. Infections occurred in 23 patients (53.5%), with 10 (23.3%) of grade ≥3. Overall, 24 patients (55.8%) had a response. Among patients treated with 320*106 CAR+ T cells and a fludarabine-, cyclophosphamide- and ALLO-647-based lymphodepletion regimen (n=24), 17 (70.8%) had a response including 11 (45.8%) with very good partial response or better and 6 (25%) with a complete response/stringent complete response. The median duration of response was 8.3months. These initial results support the feasibility and safety of allogeneic CAR T cell therapy for myeloma.

  View details for DOI 10.1038/s41591-022-02182-7

  View details for PubMedID 36690811

• Ethical challenges with multiple myeloma BCMA CAR-T slot allocation: a multi-institution experience. Transplantation and cellular therapy Kourelis, T., Bansal, R., Berdeja, J., Siegel, D., Patel, K., Mailankody, S., Htut, M., Shah, N., Wong, S. W., Sidana, S., Cowan, A. J., Alsina, M., Cohen, A., Holstein, S. A., Bergsagel, L., Ailawadhi, S., Raje, N., Dhakal, B., Rossi, A., Lin, Y. 2023

  Abstract

  CAR T cell therapies are FDA approved for patients with triple refractory multiple myeloma (MM). Real-world access to CAR T remains challenging due to supply chain limitations impacting manufacturing. The goal of this study was to evaluate the extent of this issue and how major centers are handling the challenges of CART manufacturing slot allocation. MM CAR T physician leaders at each CART treatment center across the US were surveyed. We received response from 17/20 centers. A median of one slot is allocated per month per center and the median number of patients per center on the waitlist since ide-cel approval was 20 (range 5-100). As a result, patients remained on the waitlist for a median of 6 months prior to leukapheresis (range 2-8). For patient selection, all centers reported using a committee of experienced CART physicians to ensure consistency. To ensure transparency, 15 centers make selection criteria, selection timeline and priority score readily available for CAR-T providers. Centers also reported using ethical values for selection: a) equal treatment: time spent on waiting list (n=12); b) priority to the worst-off: limited therapeutic options (n=14), MM burden (n=11), high comorbidity index (n=5); c) maximize benefit: most likely to complete apheresis (n=13) or infusion (n=13) or achieve response (n=8) and d) social value: younger pts (n=3). Maximizing benefit was considered the most important criterion by 10 centers. Our study is the first attempt to evaluate existing issues with MM CAR T access and the variability and challenges in patient selection. Integrating ethical resource allocation strategies, similar to the ones described here, into formal institutional policies would help streamline CAR-T access and protect the needs of both current and future patients and physicians.

  View details for DOI 10.1016/j.jtct.2023.01.012

  View details for PubMedID 36681151

• Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Hansen, D. K., Sidana, S., Peres, L. C., Colin Leitzinger, C., Shune, L., Shrewsbury, A., Gonzalez, R., Sborov, D. W., Wagner, C., Dima, D., Hashmi, H., Kocoglu, M. H., Atrash, S., Simmons, G., Kalariya, N., Ferreri, C., Afrough, A., Kansagra, A., Voorhees, P., Baz, R., Khouri, J., Alsina, M., McGuirk, J., Locke, F. L., Patel, K. K. 2023: JCO2201365

  Abstract

  Idecabtagene vicleucel (ide-cel) is an autologous B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy approved for relapsed/refractory multiple myeloma (RRMM) on the basis of the phase II pivotal KarMMa trial, which demonstrated best overall and ≥ complete response rates of 73% and 33%, respectively. We report clinical outcomes with standard-of-care (SOC) ide-cel under the commercial Food and Drug Administration label.Data were retrospectively collected from patients with RRMM who underwent leukapheresis as of February 28, 2022, at 11 US institutions with intent to receive SOC ide-cel. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines and managed according to each institution's policies. Responses were graded on the basis of the International Myeloma Working Group response criteria.One hundred fifty-nine of 196 leukapheresed patients received ide-cel by data cutoff. One hundred twenty (75%) infused patients would have been ineligible for participation in the KarMMa clinical trial because of comorbidities at the time of leukapheresis. Any grade and grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 82/3% and 18/6%, respectively. Best overall and ≥ complete response rates were 84% and 42%, respectively. At a median follow-up of 6.1 months from chimeric antigen receptor T infusion, the median progression-free survival was 8.5 months (95% CI, 6.5 to not reached) and the median overall survival was 12.5 months (95% CI, 11.3 to not reached). Patients with previous exposure to B-cell maturation antigen-targeted therapy, high-risk cytogenetics, Eastern Cooperative Oncology Group performance status ≥ 2 at lymphodepletion, and younger age had inferior progression-free survival on multivariable analysis.The safety and efficacy of ide-cel in patients with RRMM in the SOC setting were comparable with those in the phase II pivotal KarMMa trial despite most patients (75%) not meeting trial eligibility criteria.

  View details for DOI 10.1200/JCO.22.01365

  View details for PubMedID 36623248

• Using a Modified Delphi Panel to Estimate Health Service Utilization for Patients with Advanced and Non-Advanced Systemic Light Chain Amyloidosis. ClinicoEconomics and outcomes research : CEOR Gertz, M., Abonour, R., Gibbs, S. N., Finkel, M., Landau, H., Lentzsch, S., Lin, G., Mahindra, A., Quock, T., Rosenbaum, C., Rosenzweig, M., Sidana, S., Tuchman, S. A., Witteles, R., Yermilov, I., Broder, M. S. 2023; 15: 673-680

  Abstract

  Purpose: Patients with diagnosed with systemic light chain (AL) amyloidosis at advanced Mayo stages have greater morbidity and mortality than those diagnosed at non-advanced stages. Estimating service use by severity is difficult because Mayo stage is not available in many secondary databases. We used an expert panel to estimate healthcare utilization among advanced and non-advanced AL amyloidosis patients.Patients and Methods: Using the RAND/UCLA modified Delphi method, expert panelists completed 180 healthcare utilization estimates, consisting of inpatient and outpatient visits, testing, chemotherapy, and procedures by disease severity and organ involvement during two treatment phases (the 1 year after starting first line [1L] therapy and 1 year following treatment [post-1L]). Estimates were also provided for post-1L by hematologic treatment response (complete or very good partial response [CR/VGPR], partial, no response or relapse [PR/NR/R]). Areas of disagreement were discussed during a meeting, after which ratings were completed a second time.Results: During 1L therapy, 55% of advanced patients had ≥1 hospitalization and 38% had ≥2 admissions. Rates of hematopoietic stem cell transplant (HSCT) in advanced patients were 5%, while pacemaker or implantable cardioverter defibrillator (ICD) placement were 15%. During post-1L therapy, rates of hospitalization in advanced patients remained high (≥1 hospitalization: 20-43%, ≥2 hospitalizations: 10-20%), and up to 10% of advanced patients had a HSCT. Ten percent of these patients underwent pacemaker/ICD placement.Conclusion: Experts estimated advanced patients, who would not be good candidates for HSCT, would have high rates of hospitalization (traditionally the most expensive type of healthcare utilization) and other health service use. The development of new treatment options that can facilitate organ recovery and improve function may lead to decreased utilization.

  View details for DOI 10.2147/CEOR.S412079

  View details for PubMedID 37719133

• Prevalence, mutational spectrum and clinical implications of clonal hematopoiesis of indeterminate potential in plasma cell dyscrasias. Seminars in oncology Testa, S., Kumar, J., Goodell, A. J., Zehnder, J. L., Alexander, K. M., Sidana, S., Arai, S., Witteles, R. M., Liedtke, M. 2022

  Abstract

  Clonal hematopoiesis of indeterminate potential (CHIP) is common both in healthy individuals and patients with hematological cancers. Recent studies have showed worse prognosis for patients with multiple myeloma (MM) and non-Hodgkin lymphoma undergoing stem cell transplant, that have concomitant presence of CHIP. Data regarding the clinical and biological role of CHIP in plasma cell dyscrasias (PCDs) is rapidly increasing. However, the prevalence and prognostic implication of CHIP in patients with MM outside of the transplant setting, and in those with other more indolent PCDs remains elusive. Here we explored the prevalence and clinical implications of CHIP detected through next-generation sequencing in 209 patients with PCDs including MM, light chain (AL) amyloidosis (ALA), monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM). To avoid attributing the mutations to the plasma cell clone, CHIP was defined as the presence of DNMT3A, TET2, or ASXL1 mutations in the peripheral blood or bone marrow (DTA-CH). The prevalence of DTA-CH was 19% in patients with PCDs, with no difference between each PCD. TET2 (23%) and DNMT3A (22%), were the most frequently mutated genes. DTA-CH correlated with older age in MM (P = .001) and MGUS/SMM (P = 0.0007), as well as with coronary artery disease or congestive heart failure in MM (P = .03). DTA-CH did not predict worse OS or PFS in either MM or ALA, nor it predict higher risk of progression to MM in patients with MGUS/SMM. Our results overall further elucidate the prevalence and mutational spectrum of CHIP in PCDs, providing more information regarding the clinical relevance of CHIP in this patient population.

  View details for DOI 10.1053/j.seminoncol.2022.11.001

  View details for PubMedID 36503855

• Analysis of Bendamustine Lymphodepletion, CD19 CART Expansion, Safety and Efficacy in Patients with Rel/Ref NonHodgkin Lymphoma Bharadwaj, S., Hamilton, M. P., Sahaf, B., Tamaresis, J., Patil, S., Hanson, P. J., Latchford, T., Arai, S., Johnston, L. J., Lowsky, R., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Meyer, E. H., Shiraz, P., Sidana, S., Smith, M., Weng, W., Muffly, L., Mackall, C. L., Frank, M. J., Miklos, D. B., Dahiya, S. AMER SOC HEMATOLOGY. 2022: 10371-10373

  View details for DOI 10.1182/blood-2022-170759

  View details for Web of Science ID 000893230303169

• Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The US Myeloma CAR T Consortium Real World Experience Khouri, J., Li, H., Hansen, D. K., Sidana, S., Shune, L. O., DeJarnette, S., Anwer, F., Sborov, D. W., Wagner, C. B., Kocoglu, M., Atrash, S., Voorhees, P. M., Valent, J., Peres, L. C., Hovanky, V., Simmons, G., Dima, D., Kalariya, N., Afrough, A., Kaur, G., Sannareddy, A., Ferreri, C. J., Davis, J., McGuirk, J. P., Locke, F. L., Baz, R. C., Hamilton, B. K., Alsina, M., Sauter, C. S., Hashmi, H., Patel, K. AMER SOC HEMATOLOGY. 2022: 10427-10429

  View details for DOI 10.1182/blood-2022-163464

  View details for Web of Science ID 000893230303189

• Idecabtagene Vicleucel Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma with Renal Insufficiency: Real World Experience Sidana, S., Peres, L. C., Hashmi, H., Hosoya, H., Ferreri, C. J., Atrash, S., Khouri, J., Voorhees, P. M., Dima, D., Simmons, G., Kalariya, N., Hovanky, V., Bharadwaj, S., Arai, S., Miklos, D. B., Wagner, C. B., Davis, J., Sborov, D. W., Nishihori, T., Alsina, M., Locke, F. L., Gonzalez, R., Kocoglu, M., Sannareddy, A., Afrough, A., McGuirk, J. P., Shune, L. O., Patel, K., Hansen, D. K. AMER SOC HEMATOLOGY. 2022: 10377-10379

  View details for DOI 10.1182/blood-2022-166058

  View details for Web of Science ID 000893230303171

• Factors Associated with Refractoriness or Early Progression after Idecabtagene Vicleucel (Ide-cel) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): US Myeloma CAR T Consortium Real World Experience Hashmi, H., Hansen, D. K., Peres, L. C., Puglianini, O., Freeman, C. L., De Avila, G., Sidana, S., Shune, L. O., Sborov, D. W., Davis, J., Wagner, C. B., Kocoglu, M., Atrash, S., Voorhees, P. M., Simmons, G., Ferreri, C. J., Kalariya, N., Sannareddy, A., Dima, D., Khouri, J., McGuirk, J. P., Locke, F. L., Baz, R. C., Patel, K., Alsina, M. AMER SOC HEMATOLOGY. 2022: 4642-4645

  View details for DOI 10.1182/blood-2022-164828

  View details for Web of Science ID 000893223204292

• Racial and Ethnic Differences in Clinical Outcomes Among Multiple Myeloma Patients Treated with CAR T Therapy Peres, L. C., Oswald, L. B., Dillard, C., De Avila, G., Nishihori, T., Blue, B. J., Freeman, C. L., Locke, F. L., Alsina, M., Puglianini, O., Shune, L. O., Sborov, D. W., Wagner, C. B., Dima, D., Hashmi, H., Davis, J., Kocoglu, M., Atrash, S., Simmons, G., Kalariya, N., Ferreri, C. J., Sannareddy, A., Afrough, A., Voorhees, P. M., Khouri, J., McGuirk, J. P., Sidana, S., Hansen, D. K., Patel, K. AMER SOC HEMATOLOGY. 2022

  View details for DOI 10.1182/blood-2022-158478

  View details for Web of Science ID 000893223200252

• Universal Updated Phase 1 Data Highlights Role of Allogeneic Anti-BCMA ALLO-715 Therapy for Relapsed/Refractory Multiple Myeloma Mailankody, S., Matous, J., Liedtke, M., Sidana, S., Oluwole, O. O., Mohan, M., Cruz, J. C., Nath, R., Anwer, F., Rossi, A., Htut, M., Malik, S. A., Ghatta, S., Dillon, M., Ying, W., Navale, L., Karski, E. E., Balakumaran, A., Kumar, S. K. AMER SOC HEMATOLOGY. 2022: 4620-4622

  View details for DOI 10.1182/blood-2022-158231

  View details for Web of Science ID 000893223204284

• Disease Characterization and Response Prediction in Myeloma Patients Undergoing Conventional and Cellular Therapies from Circulating Tumor DNA Hosoya, H., Carleton, M., Tanaka, K. L., Sworder, B., Hovanky, V., Duran, G. E., Zhang, T. Y., Khodadoust, M. S., Miklos, D. B., Arai, S., Iberri, D., Liedtke, M., Sidana, S., Kurtz, D. M. AMER SOC HEMATOLOGY. 2022: 1546-1548

  View details for DOI 10.1182/blood-2022-160370

  View details for Web of Science ID 000893223201226

• Higher Rates of Severe Infection and Persistent Cytopenias in Long-Term CAR19 Responders Than after Autologous HCT: A Single Institution Study of 139 Subjects Hamilton, M. P., Liu-Fei, F. C., Alig, S. K., Tamaresis, J., Esfahani, M., Good, Z., Sworder, B., Schroers-Martin, J., Liu, C., Severinsen, F., Hanson, P. J., Lu, Y., Lowsky, R., Negrin, R. S., Meyer, E. H., Smith, M., Bharadwaj, S., Shizuru, J. A., Sidana, S., Shiraz, P., Rezvani, A. R., Johnston, L. J., Weng, W., Arai, S., Muffly, L., Dahiya, S., Diehn, M., Kurtz, D. M., Sahaf, B., Mackall, C. L., Frank, M. J., Miklos, D. B., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022: 7545-7547

  View details for DOI 10.1182/blood-2022-165600

  View details for Web of Science ID 000893230300247

• The Development of Carhlh after Axicabtagene Ciloleucel Is Associated with Poor Outcomes Philip, S., Srinagesh, H. K., Hamilton, M. P., Gentille, C., Mina, A., Arai, S., Johnston, L. J., Lowsky, R., Meyer, E. H., Negrin, R. S., Rezvani, A. R., Shiraz, P., Shizuru, J. A., Sidana, S., Weng, W., Bharadwaj, S., Dahiya, S., Muffly, L., Smith, M., Miklos, D. B., Frank, M. J. AMER SOC HEMATOLOGY. 2022: 12775-12777

  View details for DOI 10.1182/blood-2022-170877

  View details for Web of Science ID 000893230305401

• Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma. Blood advances Logue, J. M., Peres, L. C., Hashmi, H., Colin-Leitzinger, C., Shrewsbury, A. M., Hosoya, H., Gonzalez, R., Copponex, C., Kottra, K. H., Hovanky, V., Sahaf, B., Patil, S., Lazaryan, A., Jain, M. D., Baluch, A., Klinkova, O., Bejanyan, N., Faramand, R. G., Elmariah, H., Khimani, F., Davila, M. L., Mishra, A., Blue, B., Grajales-Cruz, A. F., Castaneda Puglianini, O., Liu, H., Nishihori, T., Freeman, C. L., Brayer, J., Shain, K. H., Baz, R., Locke, F. L., Alsina, M., Sidana, S., Hansen, D. K. 2022

  Abstract

  Idecabtagene vicleucel (ide-cel) was FDA approved in March 2021 for the treatment of relapsed/refractory multiple myeloma (RRMM) after 4 lines of therapy. On the KarMMa trial, grade ≥3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard of care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day 90 follow-up. Data was censored at day 100. Grade ≥3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell (pRBC) transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin (IVIG) to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 - 100 were 50% bacterial and 42% viral; only 13% were grade ≥3. On univariate analysis, high pre-CAR-T marrow myeloma burden (>/= 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥3 anemia at pre-LD were associated with grade ≥3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection.

  View details for DOI 10.1182/bloodadvances.2022008320

  View details for PubMedID 35939783

• Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed and refractory multiple myeloma: real-world experience Hansen, D., Sidana, S., Peres, L., Leitzinger, C., Shune, L., Shrewsbury, A., Gonzalez, R., Sborov, D., Wagner, C., Hashmi, H., Kocoglu, M., Atrash, S., Simmons, G., Kalariya, N., Ferreri, C., Afrough, A., Kansagra, A., Voorhees, P., Baz, R., Khouri, J., Alsina, M., McGuirk, J., Locke, F., Patel, K. CIG MEDIA GROUP, LP. 2022: S2-S3

  View details for Web of Science ID 000895909200005

• Teclistamab in Relapsed or Refractory Multiple Myeloma. The New England journal of medicine Moreau, P., Garfall, A. L., van de Donk, N. W., Nahi, H., San-Miguel, J. F., Oriol, A., Nooka, A. K., Martin, T., Rosinol, L., Chari, A., Karlin, L., Benboubker, L., Mateos, M., Bahlis, N., Popat, R., Besemer, B., Martinez-Lopez, J., Sidana, S., Delforge, M., Pei, L., Trancucci, D., Verona, R., Girgis, S., Lin, S. X., Olyslager, Y., Jaffe, M., Uhlar, C., Stephenson, T., Van Rampelbergh, R., Banerjee, A., Goldberg, J. D., Kobos, R., Krishnan, A., Usmani, S. Z. 2022

  Abstract

  BACKGROUND: Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma.METHODS: In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better).RESULTS: Among 165 patients who received teclistamab, 77.8% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell-associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2).CONCLUSIONS: Teclistamab resulted in a high rate of deep and durable response in patients with triple-class-exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.).

  View details for DOI 10.1056/NEJMoa2203478

  View details for PubMedID 35661166

• Ethical challenges with CAR T slot allocation with idecabtagene vicleucel manufacturing access. Kourelis, T., Bansal, R., Patel, K. K., Berdeja, J. G., Raje, N. S., Alsina, M., Cohen, A. D., Siegel, D., Mailankody, S., Htut, M., Sidana, S., Holstein, S. A., Cowan, A., Shah, N., Bergsagel, P., Ailawadhi, S., Lin, Y. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680304131

• Teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): Updated efficacy and safety results from MajesTEC-1. Nooka, A. K., Moreau, P., Usmani, S., Garfall, A. L., Van De Donk, N. J., San-Miguel, J. F., Oriol Rocafiguera, A., Chari, A., Karlin, L., Mateos, M., Popat, R., Martinez, J., Sidana, S., Trancucci, D., Verona, R., Girgis, S., Uhlar, C., Stephenson, T., Banerjee, A., Krishnan, A. Y. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680302046

• Idecabtagene vicleucel (Ide-cel) chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory multiple myeloma (RRMM): Real-world experience. Hansen, D. K., Sidana, S., Peres, L., Shune, L., Sborov, D. W., Hashmi, H., Kocoglu, M. H., Atrash, S., Simmons, G., Kalariya, N., Ferreri, C. J., Afrough, A., Kansagra, A. J., Voorhees, P. M., Alsina, M., McGuirk, J., Locke, F. L., Patel, K. K. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680302080

• Patient Experience in Clinical Trials: Quality of Life, Financial Burden, and Perception of Care in Patients With Multiple Myeloma or Lymphoma Enrolled on Clinical Trials Compared With Standard Care. JCO oncology practice Sidana, S., Allmer, C., Larson, M. C., Dueck, A., Yost, K., Warsame, R., Thanarajasingam, G., Cerhan, J. R., Paludo, J., Rajkumar, S. V., Habermann, T. M., Nowakowski, G. S., Lin, Y., Gertz, M. A., Witzig, T., Dispenzieri, A., Gonsalves, W. I., Ansell, S. M., Thompson, C. A., Kumar, S. K. 2022: OP2100789

  Abstract

  PURPOSE: Patients' concerns regarding clinical trial (CT) participation include apprehension about side effects, quality of life (QoL), financial burden, and quality of care.METHODS: We prospectively evaluated the experience of patients with multiple myeloma or lymphoma who were treated on CTs (CT group, n = 35) versus patients treated with standard approaches (non-CT group, n = 88) focusing on QoL, financial burden of care, and patients' perception of quality of care over a 1-year period.RESULTS: There were no significant differences in any of the patient-reported outcomes in CT versus non-CT groups. We observed an initial decline in overall QoL in the first 3 months across both groups, driven primarily by physical and functional well-being. QoL gradually improved and was above baseline by month 12. Patients reported highest improvement in the functional well-being subdomain. Patients in both groups reported high satisfaction with the quality of care received, and there were no differences in overall satisfaction, communication with team, or access to care. At baseline, 16%-19% of patients reported financial burden, which increased to a peak of 33% in the CT group and to 49% in the non-CT group over the course of 1 year. There was no significant difference in financial burden in the two groups overall. Most of the patients reported getting all the care that was deemed medically necessary in both groups. However, a significant proportion of patients reported having to make other kinds of financial sacrifices because of their cancer (CT group: 33% of patients at baseline and 21%-40% over 1 year; non-CT group: 19% at baseline and 25%-36% over 1 year).CONCLUSION: Patients treated on CTs reported comparable QoL and quality of care with the non-CT group. A high proportion of patients reported financial burden over time in both groups. Our findings can serve as a guide to educate patients regarding CT participation and highlight the need to address the significant financial burden experienced by patients with cancer.

  View details for DOI 10.1200/OP.21.00789

  View details for PubMedID 35580285

• Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia in the Modern Era. Transplantation and cellular therapy Liang, E. C., Craig, J., Torelli, S., Cunanan, K., Iglesias, M., Arai, S., Frank, M. J., Johnston, L., Lowsky, R., Meyer, E. H., Miklos, D. B., Negrin, R., Rezvani, A., Shiraz, P., Shizuru, J., Sidana, S., Weng, W. K., Bharadwaj, S., Muffly, L. 2022

  Abstract

  Allogeneic hematopoietic cell transplantation (HCT) remains an important treatment for adults with acute lymphoblastic leukemia (ALL). We hypothesized that advances in ALL and transplantation have resulted in improved HCT outcomes in recent years.To evaluate the characteristics and outcomes of adult ALL patients undergoing allogeneic HCT over the last decade.Patients with ALL aged ≥18 years old who underwent allogeneic HCT at Stanford University between 2008 and 2019 were included in this study. Patients were divided into two Eras based on year of HCT: 2008-2013 (Earlier Era) and 2014-2019 (Later Era).A total of 285 patients were included: 119 patients underwent HCT in the Earlier Era and 166 in the Later Era. Patients transplanted in the Later Era were more likely to be Hispanic (38% vs. 21%) and to have HCT-Comorbidity Index of ≥ 3 (31% vs. 18%). Donor source for HCT also differed with an increase in the use of HLA-mismatched donor sources (38% vs. 24%), notably umbilical cord blood (UCB) in the Later Era (16% vs. 0%). Patients in the Later Era were less likely to undergo transplant with active disease (4% vs.16%); pre-HCT rates of measurable residual disease (MRD) were similar across the Eras (38% vs. 40%). In unadjusted analyses, overall survival (OS) improved across Eras, with 2-year estimates for the Later and Earlier Eras of 73% (95% CI, 66%-80%) vs. 55% (95% CI, 46%-64%), respectively. Multivariable analysis confirmed the association between Later Era and OS (HR = 0.52, 95% CI, 0.34-0.78). Finally, among patients relapsing after HCT (25% in Later Era and 33% in Earlier Era), the utilization of novel immunotherapies increased in the Later Era (44% vs. 3%), as did the median OS following post-HCT relapse (16 months vs. 8 months, p < 0.001).OS following HCT for adult ALL has improved in recent years. This is due, in part, to a significant improvement in the ability to effectively salvage adults with ALL relapsing after HCT.

  View details for DOI 10.1016/j.jtct.2022.05.010

  View details for PubMedID 35584783

• Longitudinal Patient Reported Outcomes with CAR-T Cell Therapy vs Autologous and Allogeneic Stem Cell Transplant. Transplantation and cellular therapy Sidana, S., Dueck, A. C., Thanarajasingam, G., Griffin, J. M., Thompson, C., Durani, U., Burtis, M., Warsame, R., Paludo, J., Gertz, M. A., Dispenzieri, A., Ansell, S. M., Rajkumar, S. V., Yost, K., Bennani, N., Lin, Y., Kumar, S. 2022

  Abstract

  BACKGROUND: There is limited data on patient experience after chimeric antigen receptor (CAR) T cell therapy, especially in comparison to autologous and allogeneic transplant, which are more established forms of cellular therapy.OBJECTIVE: We prospectively evaluated longitudinal patient-reported quality of life (QoL), symptom burden and cognition after CAR-T cell therapy and compared it with prospective cohorts of patients undergoing autologous stem cell transplant (autoSCT) and allogeneic SCT (alloSCT).STUDY DESIGN: This was a single center study. The primary endpoint was change in QoL. Secondary endpoints were patient-reported adverse events (PRO-AEs) measured by PRO-CTCAE and cognitive function (NeuroQOLv2 questionnaire). Time profile of PRO-AEs was evaluated using longitudinal analysis Toxicity over Time (ToxT). Patients completed questionnaires at baseline, week 2 and monthly for 6 months.RESULTS: 104 patients were evaluable (CAR-T: 34, autoSCT: 33, alloSCT: 37). Baseline QoL was similar across groups. We observed a short-term decline in QoL in all groups that gradually returned to baseline. The nadir in QoL was at week 2 and coincided with peak in symptom burden. The decline in overall QoL, physical and functional well-being was significantly less with CAR-T vs. SCT groups and returned to baseline faster. Patients in the alloSCT group experienced the greatest symptom burden, greater decrease in performance status, largest short-term decline in QoL and slowest recovery.CONCLUSION: This study provides comprehensive data comparing QoL, PRO-AEs and cognition in CAR-T cell therapy vs. autoSCT and alloSCT, and the first application of ToxT to PRO-CTCAE data. Short-term QOL, including physical and functional domains was better in the CAR-T group vs. SCT groups, although all groups experienced an initial decline coinciding with peak symptoms. These data can serve as a guide for patient education, symptom management, and future studies in CAR-T cell therapy.

  View details for DOI 10.1016/j.jtct.2022.05.004

  View details for PubMedID 35550440

• Reaching beyond maximum grade: progress and future directions for modernising the assessment and reporting of adverse events in haematological malignancies. The Lancet. Haematology Thanarajasingam, G., Minasian, L. M., Bhatnagar, V., Cavalli, F., De Claro, R. A., Dueck, A. C., El-Galaly, T. C., Everest, N., Geissler, J., Gisselbrecht, C., Gormley, N., Gribben, J., Horowitz, M., Ivy, S. P., Jacobson, C. A., Keating, A., Kluetz, P. G., Kwong, Y. L., Little, R. F., Matasar, M. J., Mateos, M. V., McCullough, K., Miller, R. S., Mohty, M., Moreau, P., Morton, L. M., Nagai, S., Nair, A., Nastoupil, L., Robertson, K., Sidana, S., Smedby, K. E., Sonneveld, P., Tzogani, K., van Leeuwen, F. E., Velikova, G., Villa, D., Wingard, J. R., Seymour, J. F., Habermann, T. M. 2022; 9 (5): e374-e384

  Abstract

  Remarkable improvements in outcomes for many haematological malignancies have been driven primarily by a proliferation of novel therapeutics over the past two decades. Targeted agents, immune and cellular therapies, and combination regimens have adverse event profiles distinct from conventional finite cytotoxic chemotherapies. In 2018, a Commission comprising patient advocates, clinicians, clinical investigators, regulators, biostatisticians, and pharmacists representing a broad range of academic and clinical cancer expertise examined issues of adverse event evaluation in the context of both newer and existing therapies for haematological cancers. The Commission proposed immediate actions and long-term solutions in the current processes in adverse event assessment, patient-reported outcomes in haematological malignancies, toxicities in cellular therapies, long-term toxicity and survivorship in haematological malignancies, issues in regulatory approval from an international perspective, and toxicity reporting in haematological malignancies and the real-world setting. In this follow-up report, the Commission describes progress that has been made in these areas since the initial report.

  View details for DOI 10.1016/S2352-3026(22)00045-X

  View details for PubMedID 35483398

• Reaching beyond maximum grade: progress and future directions for modernising the assessment and reporting of adverse events in haematological malignancies LANCET HAEMATOLOGY Thanarajasingam, G., Minasian, L. M., Bhatnagar, V., Cavalli, F., De Claro, R., Dueck, A. C., El-Galaly, T. C., Everest, N., Geissler, J., Gisselbrecht, C., Gormley, N., Gribben, J., Horowitz, M., Ivy, S., Jacobson, C. A., Keating, A., Kluetz, P. G., Kwong, Y., Little, R. F., Matasar, M. J., Mateos, M., McCullough, K., Miller, R. S., Mohty, M., Moreau, P., Morton, L. M., Nagai, S., Nair, A., Nastoupil, L., Robertson, K., Sidana, S., Smedby, K. E., Sonneveld, P., Tzogani, K., van Leeuwen, F. E., Velikova, G., Villa, D., Wingard, J. R., Seymour, J. F., Habermann, T. M. 2022; 9 (5): E374-E384

  View details for Web of Science ID 000821512200012

• Updated Results From the Phase 1/2 MajesTEC-1 Study of Teclistamab, a B-Cell Maturation Antigen x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma Popat, R., Usmani, S. Z., Garfall, A., van de Donk, N., Nahi, H., San-Miguel, J. F., Oriol, A., Nooka, A., Martin, T., Rosinol, L., Chari, A., Karlin, L., Benboubker, L., Mateos, M., Bahlis, N., Moreau, P., Besemer, B., Martinez-Lopez, J., Sidana, S., Pei, L., Trancucci, D., Verona, R., Girgis, S., Olyslager, Y., Jaffe, M., Uhlar, C., Stephenson, T., Van Rampelbergh, R., Banerjee, A., Goldberg, J. D., Kobos, R., Krishnan, A. WILEY. 2022: 35-36

  View details for Web of Science ID 000776484300034

• Real-world Experience of Cryopreserved Allogeneic Hematopoietic Grafts in the COVID-19 Pandemic: A Single Center Report. Transplantation and cellular therapy Bankova, A. K., Caveney, J., Yao, B., Ramos, T. L., Bogeholz, J., Heydari, K., Diaz, N., Jackson, M. L., Lowsky, R., Brown, J. W., Johnston, L., Rezvani, A. R., Frank, M. J., Muffly, L., Weng, W., Sidana, S., Negrin, R. S., Miklos, D. B., Shiraz, P., Meyer, E. H., Shizuru, J. A., Arai, S. 1800

  Abstract

  BACKGROUND: As a result of the COVID-19 widespread pandemic, cryopreservation of allogeneic donor apheresis products was implemented to mitigate the challenges of donor availability and product transport. Although logistically beneficial, the impact of cryopreservation on clinical outcomes and graft composition remains unclear.OBJECTIVES: To compare the outcomes and graft composition with cryopreserved versus fresh allografts in the setting of allogeneic hematopoietic cell transplantation (allo-HCT).STUDY DESIGN: We retrospectively analyzed the clinical outcomes of 30 consecutive patients who received cryopreserved allografts between March and August 2020 as compared to 60 consecutive patients who received fresh allografts prior to the COVID-19 pandemic. Primary endpoints were hematopoietic engraftment, graft failure (GF) and secondary outcomes were overall survival (OS), relapse free survival (RFS) and non-relapse mortality (NRM). In addition, extended immunophenotype analysis was performed on cryopreserved versus prospectively collected fresh apheresis samples.RESULTS: Compared to fresh allografts, both neutrophil and platelet recovery were delayed in recipients of cryopreserved reduced intensity conditioning (RIC) allo-HCT with median times to engraftment of 24 days vs 18 days (P = .01) and 27 days vs 18 days (P = .069), respectively. We observed primary GF in 4 of 30 patients in the cryopreserved cohort (13.3%) vs only one of 60 patients (1.7 %) in the fresh cohort (P = .03). Cryopreserved RIC allo-HCT was associated with significantly lower median total, myeloid and T-cell donor chimerism at 1 month. OS and RFS were inferior for cryograft recipients with hazard ratio [HR (95%Cl)]: 2.16 (1.00, 4.67) and 1.90 (0.95, 3.79), respectively. Using an extended immunophenotype analysis we compared 14 samples from the cryopreserved cohort to 6 prospectively collected fresh apheresis donor samples. These analyses showed both decrease in total cell viability and significantly reduced absolute numbers of NK cells (CD3-CD56+) in the cryopreserved apheresis samples.CONCLUSION: In this single institution study we note delayed engraftment and a trend toward clinical inferiority of cryopreserved vs fresh allografts. Further evaluation of the use of cryopreserved allografts and their impact on clinical and laboratory outcomes is warranted.

  View details for DOI 10.1016/j.jtct.2022.01.010

  View details for PubMedID 35042013

• Differential Diagnosis of Waldenstr?m?s Macroglobulinemia and Early Management: Perspectives from Clinical Practice BLOOD AND LYMPHATIC CANCER-TARGETS AND THERAPY Cingam, S., Sidana, S. 2022; 12: 107-117

  Abstract

  Waldenström's Macroglobulinemia (WM) is a clonal B-lymphocyte neoplasm characterized by the presence of IgM monoclonal protein and ≥10% bone marrow involvement with lymphoplasmacytic cells. Several mature B-cell and plasma cell disorders can potentially produce monoclonal IgM immunoglobulin and hence, careful consideration of the differential diagnosis is vital. Clinico-pathological features, immunophenotype, and MYD88 mutation status help distinguish WM from other plasma cell and lymphoproliferative disorders. Treatment is only indicated in patients symptomatic from adenopathy or organomegaly, neuropathy, hyper viscosity, cryoglobulinemia, cold agglutinin disease, cytopenia's or amyloidosis. Alkylators (cyclophosphamide, bendamustine) in combination with anti-CD20 antibodies and novel targeted agents including Bruton tyrosine kinase (BTK) inhibitors like ibrutinib are the mainstay of frontline treatment in symptomatic WM.

  View details for DOI 10.2147/BLCTT.S259860

  View details for Web of Science ID 000843400400001

  View details for PubMedID 36003901

  View details for PubMedCentralID PMC9394652

• Outcomes after autologous hematopoietic cell transplantation in POEMS syndrome and comparison with multiple myeloma. Blood advances Kansagra, A., Dispenzieri, A., Fraser, R., Estrada-Merly, N., Sidana, S., Nishihori, T., Hansen, D. K., Anderson, L. D., Banerjee, R., Bumma, N., Dhakal, B., Khouri, J., Landau, H., Lee, C. H., Mian, H., Nathan, S., Savani, B. N., Kumar, S. K., Qazilbash, M. H., Shah, N., D'Souza, A. 2022

  View details for DOI 10.1182/bloodadvances.2022007218

  View details for PubMedID 35507742

• CD22-CAR T-Cell Therapy Mediates High Durable Remission Rates in Adults with Large B-Cell Lymphoma Who Have Relapsed after CD19-CAR T-Cell Therapy Frank, M. J., Baird, J. H., Patel, S., Craig, J., Spiegel, J. Y., Ehlinger, Z., Chinnasamy, H., Younes, S. F., Oak, J. S., Natkunam, Y., Reynolds, W. D., Iglesias, M., Crawford, E., Srinagesh, H. K., Egeler, E. L., Arai, S., Johnston, L. J., Lowsky, R., Negrin, R. S., Rezvani, A. R., Shiraz, P., Sidana, S., Weng, W., Schultz, L. M., Ramakrishna, S., Davis, K. L., Sahaf, B., Feldman, S. A., Mackall, C. L., Miklos, D. B., Muffl, L. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-152145

  View details for Web of Science ID 000736398803041

• Universal Updated Phase 1 Data Validates the Feasibility of Allogeneic Anti-BCMA ALLO-715 Therapy for Relapsed/Refractory Multiple Myeloma Mailankody, S., Liedtke, M., Sidana, S., Matous, J. V., Chhabra, S., Oluwole, O. O., Malik, S. A., Kumar, S., Nath, R., Anwer, F., Cruz, J., Jagannath, S., Htut, M., Raje, N. S., Siegel, D. S., Karski, E. E., Lovelace, W., Lourbakos, A., Nandakumar, S., Balakumaran, A., Hari, P. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-145572

  View details for Web of Science ID 000736398802191

• Worsening Financial Toxicity Among Patients Receiving Chimeric Antigen Receptor t-Cell (CAR-T) Therapy: A Mixed Methods Longitudinal Study Cusatis, R., Tan, I., Piehowski, C., Akinola, I., Crawford, E., Craig, J., Thiengmany, A., Frank, M. J., Miklos, D. B., Shah, N. N., D'Souza, A., Knight, J. M., Muffly, L., Flynn, K. E., Sidana, S. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-146032

  View details for Web of Science ID 000736398802108

• Do PROs Tell the Whole Story? Differential Outcomes Based on PatientReported Outcomes (PROs) Versus Performance-Based Metrics (PBM) on Cognition for Patients Receiving Chimeric Antigen Receptor (CAR)-T Cell Therapy Tan, I., Cusatis, R., Crawford, E., Thiengmany, A., Piehowski, C., Akinola, I., Craig, J., Lahijani, S., Frank, M. J., Shah, N. N., D'Souza, A., Miklos, D. B., Muffly, L., Flynn, K. E., Sidana, S. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-145746

  View details for Web of Science ID 000736413904116

• Mgta-145+Plerixafor Provides GCSFFree Rapid and Reliable Hematopoietic Stem Cell Mobilization for Autologous Stem Cell Transplant in Patients with Multiple Myeloma: A Phase 2 Study Sidana, S., Bankova, A. K., Hosoya, H., Kumar, S., Tamaresis, J., Le, A., Muffly, L., Johnston, L. J., Arai, S., Lowsky, R., Meyer, E. H., Rezvani, A. R., Weng, W., Frank, M. J., Shiraz, P., Girgenti, D., Goncalves, K. A., Schmelmer, V., Davis, J. C., Lu, Y., Shizuru, J. A., Miklos, D. B. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-149306

  View details for Web of Science ID 000736413908010

• Updated Results from MajesTEC-1: Phase 1/2 Study of Teclistamab, a B-Cell Maturation Antigen x CD3 Bispecific Antibody, in Relapsed/Refractory Multiple Myeloma Moreau, P., Usmani, S. Z., Garfall, A. L., van de Donk, N. J., Nahi, H., San-Miguel, J., Oriol, A., Nooka, A. K., Martin, T., Rosino, L., Chari, A., Karlin, L., Benboubker, L., Mateos, M., Bahlis, N. J., Popat, R., Besemer, B., Martinez-Lopez, J., Sidana, S., Pei, L., Trancucci, D., Verona, R. I., Girgis, S., Olyslager, Y., Jaffe, M., Uhlar, C. M., Stephenson, T., Van Rampelbergh, R., Banerjee, A., Goldberg, J. D., Kobos, R., Krishnan, A. Y. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-147915

  View details for Web of Science ID 000736398803193

• Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy BLOOD ADVANCES Johnsrud, A., Craig, J., Baird, J., Spiegel, J., Muffly, L., Zehnder, J., Tamaresis, J., Negrin, R., Johnston, L., Arai, S., Shizuru, J., Lowsky, R., Meyer, E., Weng, W., Shiraz, P., Rezvani, A., Latchford, T., Mackall, C., Miklos, D., Frank, M., Sidana, S. 2021; 5 (21): 4465-4475

  View details for DOI 10.1182/bloodadvances.2021004716.

  View details for Web of Science ID 000718993700016

• Concordance of peripheral blood and bone marrow measurable residual disease in adult acute lymphoblastic leukemia. Blood advances Muffly, L., Sundaram, V., Chen, C., Yurkiewicz, I., Kuo, E., Burnash, S., Spiegel, J. Y., Arai, S., Frank, M. J., Johnston, L. J., Lowsky, R., Meyer, E. H., Negrin, R. S., Rezvani, A. R., Sidana, S., Shiraz, P., Shizuru, J. A., Weng, W., Liedtke, M., Vempaty, H. T., Miklos, D. B. 2021; 5 (16): 3147-3151

  Abstract

  Monitoring of measurable residual disease (MRD) is essential to the management of acute lymphoblastic leukemia (ALL) and is typically performed through repeated bone marrow (BM) assessments. Using a next-generation sequencing (NGS) MRD platform, we performed a prospective observational study evaluating the correlation between peripheral blood (PB) and BM MRD in adults with ALL receiving cellular therapies (hematopoietic cell transplantation [HCT] and chimeric antigen receptor T-cell [CAR-T] therapies). Among the study cohort (N = 69 patients; 126 paired PB/BM samples), we found strong correlation between PB and BM MRD (r = 0.87; P < .001), with a sensitivity and specificity of MRD detection in the PB of 87% and 90%, respectively, relative to MRD in the BM. MRD became detectable in the PB in 100% of patients who subsequently relapsed following HCT, with median time from MRD+ to clinical relapse of 90 days, and in 85% of patients who relapsed following CAR T, with median time from MRD+ to clinical relapse of 60 days. In adult patients with ALL undergoing cellular therapies, we demonstrate strong concordance between NGS-based MRD detected in the PB and BM. Monitoring of ALL MRD in the PB appears to be an adequate alternative to frequent invasive BM evaluations in this clinical setting.

  View details for DOI 10.1182/bloodadvances.2021004234

  View details for PubMedID 34424318

• CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nature medicine Spiegel, J. Y., Patel, S., Muffly, L., Hossain, N. M., Oak, J., Baird, J. H., Frank, M. J., Shiraz, P., Sahaf, B., Craig, J., Iglesias, M., Younes, S., Natkunam, Y., Ozawa, M. G., Yang, E., Tamaresis, J., Chinnasamy, H., Ehlinger, Z., Reynolds, W., Lynn, R., Rotiroti, M. C., Gkitsas, N., Arai, S., Johnston, L., Lowsky, R., Majzner, R. G., Meyer, E., Negrin, R. S., Rezvani, A. R., Sidana, S., Shizuru, J., Weng, W., Mullins, C., Jacob, A., Kirsch, I., Bazzano, M., Zhou, J., Mackay, S., Bornheimer, S. J., Schultz, L., Ramakrishna, S., Davis, K. L., Kong, K. A., Shah, N. N., Qin, H., Fry, T., Feldman, S., Mackall, C. L., Miklos, D. B. 2021

  Abstract

  Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. To prevent relapse with CD19- or CD19lo disease, we tested a bispecific CAR targeting CD19 and/or CD22 (CD19-22.BB.z-CAR) in a phase I clinical trial ( NCT03233854 ) of adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility and safety with a secondary efficacy end point. Primary end points were met; 97% of products met protocol-specified dose and no dose-limiting toxicities occurred during dose escalation. In B-ALL (n=17), 100% of patients responded with 88% minimal residual disease-negative complete remission (CR); in LBCL (n=21), 62% of patients responded with 29% CR. Relapses were CD19-/lo in 50% (5 out of 10) of patients with B-ALL and 29% (4 out of 14) of patients with LBCL but were not associated with CD22-/lo disease. CD19/22-CAR products demonstrated reduced cytokine production when stimulated with CD22 versus CD19. Our results further implicate antigen loss as a major cause of CAR T cell resistance, highlight the challenge of engineering multi-specific CAR T cells with equivalent potency across targets and identify cytokine production as an important quality indicator for CAR T cell potency.

  View details for DOI 10.1038/s41591-021-01436-0

  View details for PubMedID 34312556

• Outcomes after delayed and second autologous stem cell transplant in patients with relapsed multiple myeloma. Bone marrow transplantation Lemieux, C., Muffly, L. S., Iberri, D. J., Craig, J. K., Johnston, L. J., Lowsky, R., Shiraz, P., Rezvani, A. R., Frank, M. J., Weng, W., Meyer, E., Shizuru, J. A., Arai, S., Liedtke, M., Negrin, R. S., Miklos, D. B., Sidana, S. 2021

  Abstract

  We evaluated the outcomes of 168 patients undergoing delayed or second autologous stem cell transplant (ASCT) for relapsed multiple myeloma (MM) from 2010 to 2019. Overall, 21% (n=35) patients had received a prior transplant and 69% (n=116) underwent transplant at first relapse. Overall, 27% patients had high-risk cytogenetics and 15% had ISS stage III disease. Stem cell collection was performed after relapse in 72% and 35% of patients received maintenance therapy. Median PFS from salvage treatment and transplant were 28 and 19 months, respectively. Median OS from salvage treatment and transplant was 69 and 55 months. Multivariate analysis revealed that ASCT in first relapse was associated with superior PFS (HR 0.63, p=0.03) and OS (HR 0.59, p=0.04) compared to later lines of therapy. In addition, PFS of ≥36 months with prior therapy was associated with improved PFS (HR 0.62, p=0.04) and OS (HR 0.41, p=0.01). Ninety-five patients underwent delayed transplant at first relapse, median PFS and OS from start of therapy was 30 and 69 months, and median OS from diagnosis was 106 months. These data may serve as a guide when counseling patients undergoing ASCT for relapsed MM and provide a benchmark in designing clinical trials of transplantation/comparative treatments for relapsed MM.

  View details for DOI 10.1038/s41409-021-01371-1

  View details for PubMedID 34163014

• Inferior Clinical Outcomes in Recipients of Cryopreserved Grafts Following Reduced Intensity Allogeneic Hematopoietic Cell Transplantation: A Single Center Report Bankova, A., Caveney, J., Ramos, T., Bogeholz, J., Heydari, K., Diaz, N., Jackson, M., Lowsky, R., Brown, J., Johnston, L., Rezvani, A., Frank, M., Muffly, L., Weng, W., Sidana, S., Negrin, R., Miklos, D., Shiraz, P., Meyer, E., Shizuru, J., Arai, S. SPRINGERNATURE. 2021: 181

  View details for Web of Science ID 000668928500152

• Phase 2 study of MGTA-145+plerixafor for rapid and reliable hematopoietic stem cell (HSC) mobilization for autologous transplant in multiple myeloma. Sidana, S., Bankova, A., Hosoya, H., Muffly, L. S., Kumar, S., Johnston, L. J., Lowsky, R., Meyer, E., Rezvani, A., Weng, W., Arai, S., Frank, M., Shiraz, P., Howell, H., Goncalves, K. A., Schmelmer, V., Davis, J., Shizuru, J., Miklos, D. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.8023

  View details for Web of Science ID 000708120604186

• IGVL gene region usage correlates with distinct clinical presentation in IgM vs non-IgM light chain amyloidosis. Blood advances Sidana, S., Dasari, S., Kourelis, T. V., Dispenzieri, A., Murray, D. L., King, R. L., McPhail, E. D., Ramirez-Alvarado, M., Kumar, S. K., Gertz, M. A. 2021; 5 (8): 2101–5

  Abstract

  Patients with immunoglobulin M (IgM) light chain (AL) amyloidosis have a distinct clinical presentation compared with those with non-IgM amyloidosis. We hypothesized that differential immunoglobulin light-chain variable region (IGVL) gene usage may explain the differences in organ involvement, because IGVL usage correlates with organ tropism. IGVL usage was evaluated by mass spectrometry of amyloid deposits (IgM, n = 45; non-IgM, n = 391) and differed across the 2 groups. In the lambda family, LV2-08 (13% vs 2%; P < .001) and LV2-14 (36% vs 10%; P < .001) usage was more common in IgM vs non-IgM amyloidosis, whereas LV1-44 (0% vs 10%; P = .02) and LV6-57 (2% vs 18%; P = .004) usage was less common. In the kappa family, there was a trend toward higher KV4-01 (11% vs 4%; P = .06) usage in IgM amyloidosis. IGVL usage correlated with disease characteristics/organ tropism. LV2-14 (more common in IgM amyloidosis) has historically been associated with peripheral nerve involvement and lower light chain burden, which were more frequent in IgM amyloidosis. LV1-44 (less common in IgM), associated with cardiac involvement, was less frequent in IgM patients. LV6-57 (less common in IgM) is associated with t(11;14), which was less frequent in IgM patients. In conclusion, IGVL gene usage differs in patients with IgM vs non-IgM amyloidosis and may explain the distinct clinical presentation.

  View details for DOI 10.1182/bloodadvances.2020003671

  View details for PubMedID 33877297

• Stem Cell Mobilization in Multiple Myeloma: Comparing Safety and Efficacy of Cyclophosphamide +/- Plerixafor vs. G-CSF +/- Plerixafor in the Lenalidomide Era. Transplantation and cellular therapy Johnsrud, A., Ladha, A., Muffly, L., Shiraz, P., Goldstein, G., Osgood, V., Shizuru, J. A., Johnston, L., Arai, S., Weng, W., Lowsky, R., Rezvani, A. R., Meyer, E. H., Frank, M. J., Negrin, R. S., Miklos, D. B., Sidana, S. 2021

  Abstract

  Growth factor and chemotherapy-based stem cell mobilization strategies are commonly used for patients with multiple myeloma. We retrospectively compared 398 patients mobilized between 2017-2020 using either cyclophosphamide (4g/m2) plus granulocyte colony stimulating factor (GCSF) or G-CSF alone, with on demand plerixafor (PXF) in both groups. While total CD34+yield was higher after chemo-mobilization compared to GCSF+/-PXF (median 13.6 vs. 4.4 * 106/kg,P< .01), achievement of≥2 * 106CD34+ cells (95% vs 93.7%,P= .61), and rates of mobilization failure (5% vs. 6.3%,P= .61) were similar. Fewer patients required PXF with chemo-mobilization (12.3% vs 49.5%,P< .01), and apheresis sessions were fewer (median: 1, range 1-4 vs. 2, range 1-5). Complications were higher after chemo-mobilization (30% vs. 7.4%,P< .01), including neutropenic fever, ED visits, and hospitalizations. Prior lenalidomide≤6 cycles did not impair cell yield in either group.Median cost of mobilization was 17.4% lower in the GCSF +/- PXF group (P= .01).Differences in time to engraftment were not clinically significant. Given similar rates mobilization success, engraftment time, and less toxicity and lower costs compared to chemo-mobilization, G-CSF with on-demand PXF may be preferable in myeloma patients with adequate disease control and limited lenalidomide exposure.

  View details for DOI 10.1016/j.jtct.2021.04.016

  View details for PubMedID 33915323

• Antibody-Based Treatment Approaches in Multiple Myeloma. Current hematologic malignancy reports Hosoya, H., Sidana, S. 2021

  Abstract

  PURPOSE OF REVIEW: The field of multiple myeloma treatment has entered a new era with antibody-based approaches in clinical practice. In this review, we focus on the clinical approaches of utilizing antibody-based modality, specifically monoclonal antibodies, antibody-drug conjugates, and bispecific T-cell antibodies in the treatment of multiple myeloma.RECENT FINDINGS: Three monoclonal antibodies (daratumumab, isatuximab, elotuzumab) and one anti-BCMA (B-cell maturation antigen) antibody-drug conjugate (belantamab mafodotin) have been approved by the FDA in the last 5 years for the treatment of multiple myeloma. There are many ongoing clinical trials using novel targets and constructs, including bispecific antibodies against BCMA, GPRC5D, and FCRH5. In addition to exploring efficacy, there are ongoing efforts to overcome the resistance to therapy. Antibody-based therapy has improved the outcomes of patients with multiple myeloma and has been incorporated in the standard of care. We expect to see novel targets and constructs that can achieve a deeper and more durable response while minimizing toxicity, as well as better strategies for toxicity management for existing agents. We also expect that antibody-based strategies will be used in earlier lines of therapy in the future.

  View details for DOI 10.1007/s11899-021-00624-6

  View details for PubMedID 33730360

• Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group LANCET ONCOLOGY Moreau, P., Kumar, S. K., Miguel, J., Davies, F., Zamagni, E., Bahlis, N., Ludwig, H., Mikhael, J., Terpos, E., Schjesvold, F., Martin, T., Yong, K., Durie, B. M., Facon, T., Jurczyszyn, A., Sidana, S., Raje, N., Donk, N., Lonial, S., Cavo, M., Kristinsson, S. Y., Lentzsch, S., Hajek, R., Anderson, K. C., Joao, C., Einsele, H., Sonneveld, P., Engelhardt, M., Fonseca, R., Vangsted, A., Weisel, K., Baz, R., Hungria, V., Berdeja, J. G., da Costa, F., Maiolino, A., Waage, A., Vesole, D. H., Ocio, E. M., Quach, H., Driessen, C., Blade, J., Leleu, X., Riva, E., Bergsagel, P., Hou, J., Chng, W., Mellqvist, U., Dytfeld, D., Harousseau, J., Goldschmidt, H., Laubach, J., Munshi, N. C., Gay, F., Beksac, M., Costa, L. J., Kaiser, M., Hari, P., Boccadoro, M., Usmani, S. Z., Zweegman, S., Holstein, S., Sezer, O., Harrison, S., Nahi, H., Cook, G., Mateos, M., Rajkumar, S., Dimopoulos, M. A., Richardson, P. G. 2021; 22 (3): E105–E118

  View details for Web of Science ID 000625469400010

• Use of Backup Stem Cells for Stem Cell Boost and Second Transplant in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation. Transplantation and cellular therapy Liang, E. C., Muffly, L. S., Shiraz, P., Shizuru, J. A., Johnston, L., Arai, S., Frank, M. J., Weng, W., Lowsky, R., Rezvani, A., Meyer, E. H., Negrin, R., Miklos, D. B., Sidana, S. 2021

  Abstract

  Autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient stem cells in case there is a need for stem cell boost for delayed/poor engraftment or for future second ASCT. However, collecting and storing backup stem cells in all patients requires significant resources and cost, and the rates of backup stem cell utilization are not well studied. We sought to examine the utilization of backup stem cells (BSCs) in patients with MM undergoing ASCT. Patients with MM aged ≥18 years old who underwent first ASCT at our institution from January 2010 through December 2015 and collected sufficient stem cells for at least 2 transplants were included in this single-center retrospective study. This timeframe was selected to allow for adequate follow-up. A total of 393 patients were included. The median age was 58 years (range, 25-73). After a median follow-up of 6 years, the median progression-free survival (PFS) of the cohort was 3 years. Sixty-one percent (n=240) of patients progressed or relapsed. Chemotherapy-based mobilization was used in almost all patients (98%). The median total CD34+ cells collected was 18.2*106/kg (range, 3.4-112.4). A median of 5.7*106 CD34+ cells/kg (range, 1.8-41.9) was infused during the first ASCT, and a median of 10.1*106 CD34+ cells/kg (range, 1.5-104.5) was cryopreserved for future use. Of the patients, 6.9% (n=27) used backup stem cells, with 2.3% (n=10) using them for stem cell boost, 4.6% (n=18) for a second salvage ASCT, including 1 patient for both stem cell boost and second ASCT. Rates of backup stem cell use among patients aged <60, 60-69, and ≥70 years were 7.8%, 5.7%, and 5.9%, respectively. There was a trend toward higher rates of backup stem cell use for second ASCT in patients who were younger, had suboptimal disease control at time of first ASCT, and longer PFS. The median dose of stem cell boost given was 5.6*106 CD34+ cells/kg (range, 1.9-20). The median time from stem cell boost to neutrophil, hemoglobin, and platelet engraftment was 4 (range, 2-11), 15 (range, 4-34), and 12 (range, 0-34) days, respectively. Lower CD34+ dose and older age at time of ASCT predicted need for stem cell boost. With new salvage therapies for relapsed MM, the rates of second ASCT are very low. The low rates of use suggest that institutional policies regarding universal BSC collection and long-term storage should be reassessed and individualized. However, need for stem cell boost in 2.3% of patients may present a challenge to that.

  View details for DOI 10.1016/j.jtct.2021.02.026

  View details for PubMedID 33775587

• Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma BLOOD ADVANCES Baird, J. H., Epstein, D. J., Tamaresis, J. S., Ehlinger, Z., Spiegel, J. Y., Craig, J., Claire, G. K., Frank, M. J., Muffly, L., Shiraz, P., Meyer, E., Arai, S., Brown, J., Johnston, L., Lowsky, R., Negrin, R. S., Rezvani, A. R., Weng, W., Latchford, T., Sahaf, B., Mackall, C. L., Miklos, D. B., Sidana, S. 2021; 5 (1): 143–55

  View details for DOI 10.1182/bloodadvances.2020002732

  View details for Web of Science ID 000607932700016

• Incidence and Risk Factors Associated with Bleeding and Thrombosis Following Chimeric Antigen Receptor T Cell Therapy. Blood advances Johnsrud, A. J., Craig, J., Baird, J. H., Spiegel, J. Y., Muffly, L., Zehnder, J. L., Tamaresis, J. S., Negrin, R. S., Johnston, L., Arai, S., Shizuru, J. A., Lowsky, R., Meyer, E., Weng, W. K., Shiraz, P., Rezvani, A. R., Latchford, T., Mackall, C. L., Miklos, D. B., Frank, M. J., Sidana, S. 2021

  Abstract

  Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (n=127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated between 2017-2020 with axicabtagene ciloleucel (axi-cel) (N=89) or a bispecific CD19/CD22 CAR (N=38). 12 (9.4%) and 8 (6.3%) patients developed bleeding and thrombosis within first 3 months, respectively. In the axi-cel subgroup, these occurred in 11.2% and 6.7%, respectively. Bleeding occurred between days 8-30 (median 17.5), and thrombosis between days 2-91 (median 29). Bleeding sites included genitourinary (N=6), soft tissue (N=2), intracranial (N=2), gastrointestinal (N=1), pulmonary (N=1), and were associated with features of consumptive coagulopathy. On univariate analysis, patients with bleeding were older (median 72 vs. 60 yrs, P<0.01), had lower baseline platelets (86 vs. 178 K/uL, P<0.01), lower platelet nadir after CAR-T (median 17.5 vs. 48 K/uL; P<0.01), lower fibrinogen nadir (median 122 vs. 340 ug/mL; P<0.01) and elevated LDH (P=0.01). ICANS grade ≥3 was associated with increased bleeding (50% vs. 15%; P=0.01), thrombosis (50% vs. 16%; P=0.04), PT prolongation, hypofibrinogenemia and elevated D-dimer. A paucity of events limited multivariate analysis, however low pre-treatment platelets were associated with bleeding in a multivariate logistic regression model. Patients with thrombocytopenia or severe ICANS are at increased risk of bleeding complications and should be closely monitored particularly within the first month after CAR therapy. Future studies in larger cohorts should assess risk factors for systemic coagulopathies in CAR-T therapy, including their association with neurotoxicity.

  View details for DOI 10.1182/bloodadvances.2021004716

  View details for PubMedID 34521106

• Title: Impact of Induction Therapy with VRD vs. VCD on Outcomes in Patients with Multiple Myeloma in Partial Response or Better Undergoing Upfront Autologous Stem Cell Transplantation. Transplantation and cellular therapy Sidana, S., Kumar, S., Fraser, R., Estrada-Merly, N., Giralt, S., Agrawal, V., Anderson, L. D., Aljurf, M., Banerjee, R., Bashey, A., Battiwalla, M., Beitinjaneh, A., Chakraborty, R., Chhabra, S., Dhakal, B., Dholaria, B., Hashmi, S., Janakiram, M., Lee, C., Lekakis, L., Murthy, H. S., Parrondo, R., Wangjam, T., Usmani, S., Shah, N., Qazilbash, M., D'Souza, A. 2021

  Abstract

  Bortezomib-based triplet regimens, specifically bortezomib, lenalidomide and dexamethasone (VRD) and bortezomib, cyclophosphamide and dexamethasone (VCD) are the two most common induction regimens used in transplant-eligible patients with NDMM, with conflicting data on comparative efficacy and outcomes in this population.We compared long-term outcomes of multiple myeloma (MM) patients receiving VRD vs. VCD induction prior to autologous stem cell transplant (ASCT).Patients registered with Center for International Blood and Marrow Transplant Registry were included if they underwent ASCT for MM from 01/2013 to 12/2018 within 6 months of diagnosis, received VRD or VCD induction and achieved pre-transplant > partial response. Of 1,135 patients, 914 received VRD and 221 received VCD.Patients receiving VCD were more likely to have renal impairment and ISS stage III disease and less likely to receive full dose melphalan (200 mg/m2) conditioning (69% vs 80%, p<0.001). Very good partial response rates pre-transplant, post-transplant and at best response in VRD vs. VCD were not significantly different. Maintenance use was more common after VRD (88% vs. 76%, p<0.001) with lenalidomide being the most common agent (80% vs 63%). Patients in the VRD group had higher rates of renal recovery, 74% vs. 43% p<0.001, which may be due to rapid reduction of light chains in the VRD group or improvement in renal function with VCD, which allowed switch over to VRD as patients who switched were classified in the VRD group. Patients receiving VRD had better survival on univariate analysis, with median progression-free survival (PFS) from transplant of 44.6 vs 34.1 months, p=0.004 and 5-year overall survival (OS) of 79% and 60%, p<0.001, respectively. On multivariate analysis there was no significant survival difference, with hazard ratio (VCD vs. VRD induction) for PFS being 1.22 (95% CI: 0.96-1.55, p=0.10) and OS being 1.33 (95% CI: 0.93-1.92, p=0.12). Maintenance use was independently associated with superior PFS and OS, along with ISS stage, cytogenetics and pre-transplant response (PFS only).In patients with MM undergoing upfront transplant after VRD or VCD induction, no independent survival difference was seen based on the induction therapy received after adjusting for other prognostic factors. The use of maintenance treatment was uniformly associated with superior outcomes.

  View details for DOI 10.1016/j.jtct.2021.10.022

  View details for PubMedID 34781066

• Comparison of the current renal staging, progression and response criteria to predict renal survival in AL amyloidosis using a Mayo cohort. American journal of hematology Drosou, M. E., Vaughan, L. E., Muchtar, E. n., Buadi, F. K., Dingli, D. n., Dispenzieri, A. n., Fonder, A. L., Gertz, M. A., Go, R. S., Gonsalves, W. I., Hayman, S. R., Hobbs, M. A., Hwa, Y. L., Kapoor, P. n., Kourelis, T. n., Kumar, S. n., Kyle, R. A., Lacy, M. Q., Lin, Y. n., Lopez, C. L., Lust, J. A., Rajkumar, S. V., Russell, S. J., Sidana, S. n., Siddiqui, M. A., Sidiqi, M. H., Warsame, R. n., Leung, N. n. 2021

  Abstract

  Three sets of criteria (International Society of Amyloidosis (ISA), Palladini and Kastritis) were independently developed for staging, progression and response criteria to predict renal survival in patients with AL amyloidosis. We evaluated these criteria using a cohort of 495 newly diagnosed AL amyloidosis patients with renal involvement using time to event competing risk analysis at baseline, 3, 6 and 12 months after treatment. Only Palladini and Kastritis had a staging system and both predicted a higher risk of end stage renal disease (ESRD) in the stage III vs stage I patients but only Palladini model was predictive for stage II patients. At 3 months, risk of ESRD was significantly higher for Palladini and ISA renal progression (hazard ratio (HR) 2.8 (95% CI: 1.5-5.3, p=0.001) and 2.5 (CI: 1.4-4.6, p=0.004, respectively)), but renal response was not significantly protective; conversely, the risk of ESRD was not significantly higher for the Kastritis renal progression, but was significantly protective for the Kastritis renal responders (HR 0.38 (95% CI: 0.17-0.84), p=0.017). Both progression and response with ISA, Palladini and Kastritis criteria were predictive of ESRD at 6 months and 12 months. While the Palladini staging criteria at baseline, and the ISA and Palladini criteria for progression at 3 months performed better than the Kastritis criteria at baseline and 3 months post-treatment, the Kastritis criteria performed better for response 3 months after treatment. All 3 sets of criteria performed well at and after 6 months post-treatment. These differences are important when choosing endpoints for clinical trials. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ajh.26092

  View details for PubMedID 33428787

• Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group. The Lancet. Oncology Moreau, P. n., Kumar, S. K., San Miguel, J. n., Davies, F. n., Zamagni, E. n., Bahlis, N. n., Ludwig, H. n., Mikhael, J. n., Terpos, E. n., Schjesvold, F. n., Martin, T. n., Yong, K. n., Durie, B. G., Facon, T. n., Jurczyszyn, A. n., Sidana, S. n., Raje, N. n., van de Donk, N. n., Lonial, S. n., Cavo, M. n., Kristinsson, S. Y., Lentzsch, S. n., Hajek, R. n., Anderson, K. C., João, C. n., Einsele, H. n., Sonneveld, P. n., Engelhardt, M. n., Fonseca, R. n., Vangsted, A. n., Weisel, K. n., Baz, R. n., Hungria, V. n., Berdeja, J. G., Leal da Costa, F. n., Maiolino, A. n., Waage, A. n., Vesole, D. H., Ocio, E. M., Quach, H. n., Driessen, C. n., Bladé, J. n., Leleu, X. n., Riva, E. n., Bergsagel, P. L., Hou, J. n., Chng, W. J., Mellqvist, U. H., Dytfeld, D. n., Harousseau, J. L., Goldschmidt, H. n., Laubach, J. n., Munshi, N. C., Gay, F. n., Beksac, M. n., Costa, L. J., Kaiser, M. n., Hari, P. n., Boccadoro, M. n., Usmani, S. Z., Zweegman, S. n., Holstein, S. n., Sezer, O. n., Harrison, S. n., Nahi, H. n., Cook, G. n., Mateos, M. V., Rajkumar, S. V., Dimopoulos, M. A., Richardson, P. G. 2021; 22 (3): e105–e118

  Abstract

  This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.

  View details for DOI 10.1016/S1470-2045(20)30756-7

  View details for PubMedID 33662288

• Outcomes with different administration schedules of Bortezomib in Bortezomib, Lenalidomide and dexamethasone (VRd) as first-line therapy in Multiple Myeloma. American journal of hematology Cook, J., Johnson, I., Higgins, A., Sidana, S., Warsame, R., Gonsalves, W., Gertz, M. A., Buadi, F., Lacy, M., Kapoor, P., Dispenzieri, A., Kourelis, T., Dingli, D., Amie Fonder, P. A., Hayman, S., Hobbs, M., Hwa, Y. L., Kyle, R., Leung, N., Go, R., Rajkumar, V. S., Kumar, S. 2020

  Abstract

  Induction therapy for multiple myeloma with bortezomib (V), lenalidomide (R), and dexamethasone (d) (VRd) was traditionally administered as bortezomib given twice weekly on a 3 week cycle. A modified schedule of weekly bortezomib has been adopted over time to decrease treatment burden for patients and reduce treatment-emergent neuropathy. This study evaluates the response rates and outcomes with different schedules of bortezomib in VRd administered for first-line treatment for patient with newly diagnosed MM (NDMM). We retrospectively analyzed patients treated with upfront VRd from June 30th 2008 to December 31st 2018 for variations of bortezomib administration. Five hundred and fifty five (555) NDMM patients met inclusion criteria; median age 63years and 61% men. Bortezomib was administered twice weekly every 21days in 42%, once weekly every 21days in 41% and once weekly every 28days in 16%. Though peripheral sensory neuropathy was more frequent with twice weekly dosing (p=0.002), this group achieved shorter time to best response (p=0.01). Weekly every 21 day treatment saw higher VGPR or better rates (p=0.02). However, with median follow up time of 37 months (IQR 22-56), we found no difference in PFS or OS among the groups. While small differences in response rates were found among the varying administration schedules of bortezomib administration, there was no significant effect on PFS or OS. Given that VRd remains a first line standard of care option for newly diagnosed MM, in the absence of a large trial comparing bortezomib dosing schedule modifications, these results are helpful in supporting current practices of once weekly administration. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ajh.26074

  View details for PubMedID 33326116

• Outcomes with Autologous or Allogeneic Stem Cell Transplantation in Patients with Plasma Cell Leukemia in the Era of Novel Agents. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Lemieux, C., Johnston, L. J., Lowsky, R., Muffly, L. S., Craig, J. K., Shiraz, P., Rezvani, A., Frank, M. J., Weng, W., Meyer, E., Shizuru, J., Arai, S., Negrin, R., Miklos, D. B., Sidana, S. 2020

  Abstract

  Plasma cell leukemia (PCL) is a rare and very aggressive plasma cell disorder. The optimal treatment approach, including whether to pursue an autologous (autoSCT) or allogeneic (alloSCT) transplant is not clear as there is lack of clinical trial based evidence. This single center retrospective study describes the outcomes of 16 patients with PCL (N=14 primary PCL) who underwent either autoSCT (N=9) or alloSCT (N=7) for PCL in the era of novel agents, between 2007 and 2019. Median age of the cohort was 58 years. High-risk cytogenetics were seen in 50% of patients. All patients received a proteasome inhibitor (PI) and/or immunomodulatory drug (IMiD) based regimen before transplant. At transplant, 10 (62%) patients obtained at least a very good partial response. Response after autoSCT (3 month) was at least VGPR in 6 (67%, CR=5) patients. All patients undergoing alloSCT achieved CR at 3 months. Maintenance was used in 5 patients (56%) after autoSCT. Median PFS from transplant in the autoSCT vs. alloSCT group was 6 vs. 18 months, p=0.09, while median OS from transplant was 19 vs. 40 months (p=0.41), respectively. The median OS from diagnosis was 27 vs. 49 months, p=0.50, respectively. Of all the deaths, 10 (91%) patients died of relapsed disease. In conclusion, alloSCT was not observed to offer any significant survival advantage over autoSCT in PCL, which is comparable to other recent reports and relapse remains the primary cause of death.

  View details for DOI 10.1016/j.bbmt.2020.08.035

  View details for PubMedID 32961371

• International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials. Leukemia Costa, L. J., Derman, B. A., Bal, S., Sidana, S., Chhabra, S., Silbermann, R., Ye, J. C., Cook, G., Cornell, R. F., Holstein, S. A., Shi, Q., Omel, J., Callander, N. S., Chng, W. J., Hungria, V., Maiolino, A., Stadtmauer, E., Giralt, S., Pasquini, M., Jakubowiak, A. J., Morgan, G. J., Krishnan, A., Jackson, G. H., Mohty, M., Mateos, M. V., Dimopoulos, M. A., Facon, T., Spencer, A., Miguel, J. S., Hari, P., Usmani, S. Z., Manier, S., McCarthy, P., Kumar, S., Gay, F., Paiva, B. 2020

  Abstract

  Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

  View details for DOI 10.1038/s41375-020-01012-4

  View details for PubMedID 32778736

• Outcomes with early vs. deferred stem cell transplantation in light chain amyloidosis. Bone marrow transplantation Abdallah, N., Sidana, S., Dispenzieri, A., Lacy, M., Buadi, F., Hayman, S., Kapoor, P., Leung, N., Dingli, D., Hwa, Y. L., Lust, J., Russell, S., Gonsalves, W., Go, R., Hogan, W., Kyle, R., Rajkumar, S. V., Gertz, M., Kumar, S. 2020

  Abstract

  In the presence of effective treatment options for systemic light chain (AL) amyloidosis, autologous stem cell transplantation (ASCT) is sometimes deferred after stem cell collection. We designed this retrospective study to compare overall survival (OS) between patients who proceed directly to ASCT after stem cell collection and those who defer ASCT. We included patients with AL amyloidosis who had stem cell collection at Mayo Clinic, Minnesota, from 2004 to 2018. ASCT was considered "early" if performed within 90 days of collection, and "deferred" if performed after 90 days, or not done by last follow up. We included 651 patients; 527 underwent early ASCT and 124 deferred ASCT. There was no difference in OS with early vs. deferred ASCT (median OS: 13.0 vs. 11.4 years, respectively, P=0.28). There was no difference in OS between the 2 groups among patients with early or advanced Mayo Stage. Among patients who achieved ≥very good partial response at the time of collection, OS in the early and deferred groups was 14.2 and 13.4 years, respectively (P=0.06). Survival outcomes are similar with early and deferred ASCT. Further studies are needed to identify patients who would benefit from each approach.

  View details for DOI 10.1038/s41409-020-0964-8

  View details for PubMedID 32518290

• Quality of life (QOL), financial burden, and perception of care in patients enrolled on clinical trials (CTs). Sidana, S., Allmer, C., Larson, M. C., Dueck, A. C., Yost, K. J., Warsame, R. M., Thanarajasingam, G., Cerhan, J., Paludo, J., Rajkumar, S., Habermann, T., Nowakowski, G. S., Lin, Y., Gertz, M. A., Witzig, T. E., Dispenzieri, A., Gonsalves, W., Ansell, S. M., Thompson, C. A., Kumar, S. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368307086

• Impact of proteasome inhibitor vs. IMiD maintenance therapy on outcomes of patients with high-risk multiple myeloma (HRMM). Tam, E., Iberri, D., Liedtke, M., Muffly, L. S., Shiraz, P., Frank, M., Lowsky, R., Rezvani, A., Negrin, R., Meyer, E., Arai, S., Johnston, L. J., Shizuru, J., Weng, W., Miklos, D., Sidana, S. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368307484

• Glycosylation of Immunoglobulin Light Chains is Highly Prevalent in Cold Agglutinin Disease. American journal of hematology Sidana, S., Murray, D. L., Dasari, S., Go, R. S., Muchtar, E., Willrich, M. A., Snyder, M., Kohlhagen, M., Lust, J. A., Kourelis, T. V., Kumar, S. K., Dispenzieri, A., Gertz, M. A. 2020

  View details for DOI 10.1002/ajh.25843

  View details for PubMedID 32356376

• A validated composite organ and hematologic response model for early assessment of treatment outcomes in light chain amyloidosis. Blood cancer journal Sidana, S., Milani, P., Binder, M., Basset, M., Tandon, N., Foli, A., Dispenzieri, A., Gertz, M. A., Hayman, S. R., Buadi, F. K., Lacy, M. Q., Kapoor, P., Leung, N., Rajkumar, S. V., Merlini, G., Palladini, G., Kumar, S. K. 2020; 10 (4): 41

  Abstract

  Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n=473; validation cohort, Pavia: n=575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using incremental scoring based on hazard ratios with scores of 0-3 for HR (0-CR, 1-VGPR, 2-PR, 3-no response) and 0-2 for OR (0-AOR, 1-MOR, 2-NOR). Patients could be divided into two distinct CHOR groups (scores 0-3 and 4-5), with median OS in group 1 and group 2: Not reached vs. 34 months, p<0.001 [Mayo] and 87 vs. 23 months, p<0.001 [Pavia]. In conclusion, we developed a model that can assess multiple organs concurrently, and integrate both HR and OR assessments to determine early clinical benefit with treatment, which may be used as a surrogate end-point in trials and to compare outcomes with different therapies.

  View details for DOI 10.1038/s41408-020-0306-5

  View details for PubMedID 32286270

• Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia: Significant Increase in Survival in the Post-Targeted Immunotherapy Era Muffly, L., Arai, S., Johnston, L., Lowsky, R., Meyer, E. H., Miklos, D. B., Negrin, R. S., Rezvani, A., Shiraz, P., Shizuru, J. A., Sidana, S., Weng, W., Cunanan, K. ELSEVIER SCIENCE INC. 2020: S106

  View details for Web of Science ID 000516887900144

• Impact of Minimal Residual Negativity using Next Generation Flow Cytometry on Outcomes in Light Chain Amyloidosis. American journal of hematology Sidana, S., Muchtar, E., Sidiqi, M. H., Jevremovic, D., Dispenzieri, A., Gonsalves, W., Buadi, F., Lacy, M. Q., Hayman, S. R., Kourelis, T., Kapoor, P., Go, R. S., Warsame, R., Leung, N., Rajkumar, S. V., Kyle, R. A., Gertz, M. A., Kumar, S. K. 2020

  Abstract

  We evaluated bone marrow minimal residual disease (MRD) negativity in 44 patients with light chain (AL) amyloidosis using next generation flow cytometry (sensitivity > 1x 10-5 ; median events analyzed: 8.7 million, range: 4.8 to 9.7 million). All patients underwent MRD testing in two years from start of therapy (median: 7 months). Overall MRD negative rate was 64% (n=28). MRD-negative rate after one-line of therapy was 71% (20/28). MRD negative rates were higher with stem-cell transplant as first-line therapy (86%, 18/21) vs. chemotherapy alone as first-line treatment (29%, 2/7), p=0.005. MRD negative rate amongst patients in complete response were 75% (15/20); in very good partial response: 50% (11/22) and there were two patients in partial response/rising light chains (with renal dysfunction) who were MRD negative. There were no differences in baseline characteristics of MRD negative vs. MRD positive patients, except younger age among MRD-negative patients. MRD negative patients were more likely to have achieved cardiac response at the time of MRD assessment, 67% (8/12) vs. 22% (2/7), p=0.04. Renal response rates were similar in both groups. Progression free survival was assessed in the 42 patients achieving CR or VGPR. After median follow-up of 14 months, the estimated 1-year progression free survival in MRD negative vs. MRD positive patients was 100% (26 patients, 0 events) vs. 64% (16 patients, 5 events), p=0.006, respectively. MRD assessment should be explored as a surrogate endpoint in clinical trials and MRD risk-adapted trials may help optimize treatment in AL amyloidosis. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ajh.25746

  View details for PubMedID 32010993

• Organ responses with daratumumab therapy in previously treated AL amyloidosis. Blood advances Chung, A. n., Kaufman, G. P., Sidana, S. n., Eckhert, E. n., Schrier, S. L., Lafayette, R. A., Arai, S. n., Witteles, R. M., Liedtke, M. n. 2020; 4 (3): 458–66

  Abstract

  Immunoglobulin light chain amyloidosis (AL amyloidosis) involves deposition of abnormally folded light chains into a wide range of tissues causing organ dysfunction, including in the heart and kidney. Daratumumab, a CD38-targeted antibody, has recently demonstrated efficacy in producing hematologic responses in previously treated disease. However, data on survival outcomes and organ responses to daratumumab are lacking. Seventy-two patients with previously treated AL amyloidosis who received daratumumab monotherapy with dexamethasone were retrospectively evaluated. With a median follow-up of 27 months, 2-year overall survival (OS) was 86.9% (median OS, not reached) and 2-year time-to-next treatment or death (TTNT)-free survival was 62% (median TTNT, not reached). Forty of 52 evaluable patients achieved a hematologic response (77%), with >60% of patients achieving a very good partial response or better; median time-to-hematologic response was 1 month. Fifty-seven patients (79%) had cardiac involvement, and 55% of evaluable patients achieved a cardiac response, with a median response time of 3.2 months among responders. Cardiac responses were associated with an improvement in OS, with landmark analysis for cardiac responses at 3 months trending toward statistical significance (100% vs 55% at 30 months, P = .051). Forty-seven patients (65%) had renal involvement, and 52% of evaluable patients achieved a renal response, with a median response time of 6 months among responders; there was no significant difference in OS between renal responders and nonresponders. This study demonstrates that daratumumab is highly effective in the treatment of previously treated AL amyloidosis, and a significant proportion of patients can achieve deep hematologic responses, as well as improvements in organ function.

  View details for DOI 10.1182/bloodadvances.2019000776

  View details for PubMedID 32027745

• Outcomes with autologous stem cell transplant vs. non-transplant therapy in patients 70 years and older with multiple myeloma. Bone marrow transplantation Lemieux, C. n., Muffly, L. S., Rezvani, A. n., Lowsky, R. n., Iberri, D. J., Craig, J. K., Frank, M. J., Johnston, L. J., Liedtke, M. n., Negrin, R. n., Weng, W. K., Meyer, E. n., Shizuru, J. n., Shiraz, P. n., Arai, S. n., Miklos, D. B., Sidana, S. n. 2020

  Abstract

  We evaluated 79 patients with multiple myeloma (MM) ≥70 years referred to our blood and marrow transplant clinic, within 1 year of diagnosis from 2010 to 2019, for consideration of autologous stem cell transplant (ASCT). Thirty-eight (48%) of 79 patients underwent ASCT. ASCT was not pursued in 41 (52%) patients due to: patient or physician preference in 80% (n = 33) or ineligibility in 20% (n = 8). Baseline characteristics of patients in the two groups were similar. Median PFS from treatment start amongst patients undergoing ASCT (n = 38) vs. not (n = 41) was 41 months vs. 33 months, p = 0.03. There was no difference in OS, with estimated 5-year OS of 73% vs. 83%, respectively (p = 0.86). Day +100 transplant-related mortality (TRM) was 0%. ASCT was an independent favorable prognostic factor for PFS in multivariate analysis, after accounting for HCT-CI score, performance status, hematologic response, and maintenance. Finally, patients ≥70 years undergoing ASCT had similar PFS compared to a contemporaneous institutional cohort of patients <70 years (n = 631) (median PFS from transplant: 36 vs. 47 months, p = 0.25). In this retrospective analysis, ASCT was associated with low TRM and better PFS in fit older adults with MM compared to non-transplant therapy, with comparable benefits as seen in younger patients.

  View details for DOI 10.1038/s41409-020-01026-7

  View details for PubMedID 32782351

• CD22-Directed CAR T-Cell Therapy Induces Complete Remissions in CD19-Directed CAR-Refractory Large B-Cell Lymphoma. Blood Baird, J. H., Frank, M. J., Craig, J. n., Patel, S. n., Spiegel, J. Y., Sahaf, B. n., Oak, J. S., Younes, S. n., Ozawa, M. n., Yang, E. n., Natkunam, Y. n., Tamaresis, J. S., Ehlinger, Z. n., Reynolds, W. D., Arai, S. n., Johnston, L. n., Lowsky, R. n., Meyer, E. n., Negrin, R. S., Rezvani, A. R., Shiraz, P. n., Sidana, S. n., Weng, W. K., Davis, K. L., Ramakrishna, S. n., Schultz, L. n., Mullins, C. D., Jacob, A. P., Kirsch, I. R., Feldman, S. A., Mackall, C. L., Miklos, D. B., Muffly, L. n. 2020

  Abstract

  The prognosis for patients with large B-cell lymphoma (LBCL) progressing after treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CAR19) is poor. We report on the first three consecutive patients with autologous CAR19-refractory LBCL treated with a single infusion of autologous 1×106 CAR+ T-cells/kg targeting CD22 (CAR22) as part of a phase I dose escalation study. CAR22 therapy was relatively well tolerated, without any observed non-hematologic adverse events higher than grade 2. Following infusion, all three patients achieved complete remission, with all responses ongoing at the time of last follow up (mean 7.8 months, range 6-9.3). Circulating CAR22 cells demonstrated robust expansion (peak range 85.4-350 cells/µL), and persisted beyond three months in all patients with continued radiographic responses and corresponding decreases in circulating tumor DNA (ctDNA) beyond six months post-infusion. Further accrual at a higher dose level in this phase 1 dose-escalation study is ongoing and will explore the role of this therapy in patients who have failed prior CAR T-cell therapies. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT04088890).

  View details for DOI 10.1182/blood.2020009432

  View details for PubMedID 33512414

• Evidence-Based Minireview: Does achieving MRD negativity after initial therapy improve prognosis for high-risk myeloma patients? Sidana, S., Manasanch, E. AMER SOC HEMATOLOGY. 2019: 142–47

  View details for Web of Science ID 000538564000020

• CAR T-cell therapy: is it prime time in myeloma? Sidana, S., Shah, N. AMER SOC HEMATOLOGY. 2019: 260–65

  View details for Web of Science ID 000538564000038

• Revisiting complete response in light chain amyloidosis. Leukemia Sidana, S., Dispenzieri, A., Murray, D. L., Go, R. S., Buadi, F. K., Lacy, M. Q., Gonsalves, W. I., Dingli, D., Warsame, R., Kourelis, T., Muchtar, E., Hayman, S. R., Kapoor, P., Kyle, R. A., Leung, N., Rajkumar, S. V., Gertz, M. A., Kumar, S. K. 2019

  View details for DOI 10.1038/s41375-019-0664-9

  View details for PubMedID 31772296

• Bone marrow plasma cells 20% or greater discriminate presentation, response, and survival in AL amyloidosis. Leukemia Muchtar, E., Gertz, M. A., Kourelis, T. V., Sidana, S., Go, R. S., Lacy, M. Q., Buadi, F. K., Dingli, D., Hayman, S. R., Kapoor, P., Leung, N., Fonder, A., Hobbs, M., Lisa Hwa, Y., Gonsalves, W., Warsame, R., Russell, S., Lust, J. A., Lin, Y., Zeldenrust, S., Rajkumar, S. V., Kyle, R. A., Kumar, S. K., Dispenzieri, A. 2019

  Abstract

  We explored the association between bone marrow plasma cells (BMPCs) and disease presentation and outcome among 1574 AL patients. Three BMPC groups were formulated: <5% (n=231, 15% of study population), 5-19% (n=1045, 66%), and ≥20% (n=298, 19%). Heart and renal involvement were more and less prevalent, respectively, with increasing BMPCs. Patients with ≥20% BMPCs had higher likelihood for classic myeloma phenotype with less skewed lambda restriction, a higher rate of intact immunoglobulin secretion, a lower hemoglobin and higher rates of hypercalcemia and bone lytic lesions. High-risk cytogenetic abnormalities were more common in ≥20% BMPCs. Complete hematological response was less frequent with rising BMPCs. The median survival was inversely associated with the BMPC groups (81, 33, 12 months for <5%, 5-19%, and ≥20% BMPCs, respectively; P<0.001). Survival discrimination was maintained at 1-year landmark and in those who achieved a complete response. Multivariate analysis accounting for known prognostic markers yielded an independent prognostic role for ≥20% BMPCs, but not for the other BMPC groups. AL patients with 20% or greater BMPCs have poorer outcome independent of their cardiac risk category and stem cell transplant eligibility. Distinct interventions in these patients should be explored to improve outcome.

  View details for DOI 10.1038/s41375-019-0655-x

  View details for PubMedID 31758090

• Long-Term Outcomes and Organ Responses with Daratumumab Therapy in Previously Treated Patients with AL Amyloidosis Chung, A., Kaufman, G. P., Sidana, S., Eckhert, E., Schrier, S., Arai, S., Lafayette, R., Witteles, R., Liedtke, M. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-122152

  View details for Web of Science ID 000577160403100

• Patient Experience of Chimeric Antigen Receptor (CAR)-T Cell Therapy Vs. Stem Cell Transplant: Longitudinal Patient Reported Adverse Events, Cognition and Quality of Life Sidana, S., Thanarajasingam, G., Griffin, J., Thompson, C. A., Burtis, M., Warsame, R., Paludo, J., Cheville, A., Gertz, M. A., Dispenzieri, A., Villasboas, J., Ansell, S. M., Rajkumar, S., Yost, K. J., Bennani, N., Siddiqui, M., Lin, Y., Kumar, S. K., Dueck, A. C. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-121715

  View details for Web of Science ID 000518218500863

• Glycosylation of Immunoglobulin Light Chains Is Highly Prevalent in Cold Agglutinin Disease Sidana, S., Murray, D. L., Dasari, S., Go, R. S., Willrich, M., Snyder, M., Kohlhagen, M., Lust, J. A., Muchtar, E., Kourelis, T., Kumar, S. K., Dispenzieri, A., Gertz, M. A. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-121712

  View details for Web of Science ID 000577164600090

• Immunoglobulin Variable Gene Region (IGVL) Usage Correlates with Distinct Clinical Presentation in IgM Versus Non-IgM Light Chain Amyloidosis Sidana, S., Dasari, S., Kourelis, T., Dispenzieri, A., Murray, D. L., King, R. L., McPhail, E. D., Ramirez-Alvarado, M., Kumar, S. K., Gertz, M. A. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-121714

  View details for Web of Science ID 000577160403042

• Favorable Long-Term Outcomes after Daratumumab Discontinuation in AL Amyloidosis Patients Achieving Deep Responses Chung, A., Kaufman, G. P., Sidana, S., Iberri, D., Eckhert, E., Schrier, S., Lafayette, R., Arai, S., Witteles, R., Liedtke, M. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-124981

  View details for Web of Science ID 000577160403156

• Impact of consolidation therapy post autologous stem cell transplant in patients with light chain amyloidosis AMERICAN JOURNAL OF HEMATOLOGY Al Saleh, A. S., Sidiqi, M., Sidana, S., Muchtar, E., Dispenzieri, A., Dingli, D., Lacy, M. Q., Warsame, R. M., Gonsalves, W. I., Kourelis, T. V., Hogan, W. J., Hayman, S. R., Wolf, R. C., Kapoor, P., Buadi, F. K., Kumar, S. K., Gertz, M. A. 2019: 1066–71

  Abstract

  The role of consolidation post autologous stem cell transplant in light chain amyloidosis is not well defined. We retrospectively identified patients who had light chain amyloidosis and underwent autologous stem cell transplant at the Mayo Clinic. Consolidation was defined as any treatment given after the day 100 evaluation post-transplant to maintain or deepen the response. We identified 471 patients, of whom 72 (15%) received consolidation. Patients receiving consolidation had more advanced disease (Mayo 2012 stage ≥II in 67% vs 52%, P = .02), and had lower day 100 response rates (very good partial response or better: 35% vs 84%, P < .001). After consolidation, rates of very good partial response improved from 24% to 28%, and rates of complete response improved from 11% to 40%. Patients with less than very good partial response who received consolidation, had better progression-free survival (median of 22.4 vs 8.8 months, P < .001), and the benefit was greater in those who deepened their response (median of 41 vs 8.8 months, P < .001). In patients with less than very good partial response, there was a trend for better overall survival in patients who responded to consolidation (median of 125.8 vs 74.4 months, P = .07). In patients who achieved very good partial response, or better, at day 100 post autologous stem cell transplant, consolidation did not improve progression-free or overall survival. Consolidation after autologous stem cell transplant for light chain amyloidosis improves progression-free survival for patients who achieve less than very good partial response.

  View details for DOI 10.1002/ajh.25572

  View details for Web of Science ID 000477399700001

  View details for PubMedID 31273808

• Fifteen year overall survival rates after autologous stem cell transplantation for AL amyloidosis AMERICAN JOURNAL OF HEMATOLOGY Sidana, S., Sidiqi, M., Dispenzieri, A., Buadi, F. K., Lacy, M. Q., Muchtar, E., Dingli, D., Haynnan, S. R., Gonsalves, W., Kapoor, P., Leung, N., Warsame, R., Kourelis, T., Wolf, R. C., Hogan, W. J., Kumar, S. K., Gertz, M. A. 2019

  Abstract

  In appropriately selected patients with AL amyloidosis, autologous stem cell transplant (ASCT) is an established treatment modality with excellent outcomes and decreasing transplant related mortality (TRM) over time. We report on 15-year overall survival (OS) in 159 patients undergoing ASCT from 1996 to 2003, with median follow up of 17.1 years. Day 100 TRM was 13.2% (n = 21). The OS of ≥15 years was observed in 30% (47/159) of patients. Patients surviving ≥15 years were younger (53 vs 56 years, P = .02), less likely to have lambda as the involved light chain (62% vs 78%, P = .03) and were less likely to have heart involvement (32% vs 56%, P = .005). Median OS of patients with heart involvement vs not was 4.0 vs 11.1 years, P = .006 and actuarial 15-year OS was 23% vs 43%, respectively. A higher proportion of patients with OS ≥15 years received full-dose melphalan conditioning (81% vs 61%, P = .01), and achieved day 100 complete response (CR) (64% vs 24%, P < .001). Median OS amongst patients who achieved CR vs not was 19.3 vs 5.4 years, P < .001. Heart involvement, receiving full-dose melphalan and achieving CR remained independent predictors of OS. AL amyloidosis and related complications were the cause of death in 52% of patients overall (1-5 years post-transplant: 81%; 5-10 years: 62% and 10-15 years: 55%). These results reinforce the key role of ASCT in AL amyloidosis. With improvements in TRM and more options for relapsed disease, we expect the long-term survival post-transplant to improve significantly in the future.

  View details for DOI 10.1002/ajh.25566

  View details for Web of Science ID 000474995300001

  View details for PubMedID 31254301

• Clinical features, laboratory characteristics and outcomes of patients with renal versus cardiac light chain amyloidosis BRITISH JOURNAL OF HAEMATOLOGY Sidana, S., Tandon, N., Gertz, M. A., Dispenzieri, A., Ramirez-Alvarado, M., Murray, D. L., Kourelis, T. V., Buadi, F. K., Kapoor, P., Gonsalves, W., Warsame, R., Lacy, M. Q., Kyle, R. A., Rajkumar, S., Kumar, S. K., Leung, N. 2019; 185 (4): 701–7

  Abstract

  This study evaluated the differences in clinical features of 1077 newly diagnosed AL amyloidosis patients with renal involvement (n = 229, 21%), both cardiac and renal involvement (n = 443, 41%) and cardiac involvement (n = 405, 38%). Significant differences in dFLC (difference in involved and uninvolved light chains) were noted (renal, both, cardiac median: 83, 234 and 349 mg/l, P < 0.001). The proportion of patients with ≥ 10% bone marrow plasma cells (BMPCs) was lowest in renal only patients: 44%, 57%, 64%, respectively, P < 0.001. In a multivariate linear regression model incorporating organ involvement type and BMPCs ≥10%, organ involvement was a significant predictor of dFLC (P < 0.001). Median overall survival (OS) across the three groups was 83 vs. 19 vs. 16 months (P < 0.001) in patients not undergoing transplant and 5-year OS in patients undergoing transplant was 90% vs. 75% vs. 64% (P = 0.007), respectively. In conclusion, renal involvement alone or renal + cardiac involvement in AL amyloidosis is associated with lower circulating light chain burden, which cannot be fully explained by BMPC burden alone. Increased sensitivity of the kidney to light chains, given significant interactions with the renal tubular system and secretion of modified light chain products may play a role in pathogenesis of renal AL amyloidosis and warrants further investigation.

  View details for DOI 10.1111/bjh.15832

  View details for Web of Science ID 000467276100009

  View details for PubMedID 30836444

• Patient-Reported Outcomes with Chimeric Antigen Receptor T Cell Therapy: Challenges and Opportunities. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Chakraborty, R., Sidana, S., Shah, G. L., Scordo, M., Hamilton, B. K., Majhail, N. S. 2019; 25 (5): e155–e162

  Abstract

  Patient-reported outcomes (PROs) are an important tool to assess the impact of a new therapy on symptom burden and health-related quality of life (HRQoL). Chimeric antigen receptor T (CAR-T) cell therapies have been approved for use in relapsed or refractory leukemia and lymphoma based on promising efficacy in clinical trials. However, data are lacking on patient-reported toxicity and impact on HRQoL. This review provides an overview of the incorporation of PROs in CAR-T cell therapy and the specific challenges in this context. The first step is to demonstrate feasibility of PRO monitoring in the acute phase after CAR-T cell infusion. Apart from core PRO domains like physical functioning, disease-related symptoms, and symptomatic adverse effects, important measures to consider are cognitive functioning and financial toxicity. Because there are no validated PRO instruments in the setting of CAR-T cell therapy, universally validated measures like Patient-Reported Outcomes Measurement Information System (PROMIS) could be considered, which is also recommended in the setting of hematopoietic stem cell transplantation. Given the timeline of toxicities with CAR-T cell therapy, PRO instruments should be administered at baseline and at least weekly in the first 30 days. Subsequently, frequent monitoring of PROs in the first year might be helpful in identifying short- and intermediate-term toxicities, functional limitations, and neuropsychiatric effects. The major potential challenge in acute phase would be missing data when patients develop severe cytokine release syndrome or neurotoxicity. Designing a strategy for handling missing data is crucial. The long-term safety of CAR-T cell therapy is not well characterized because of short follow-up in most studies reported thus far. PROs should be measured at least yearly after the first year to identify potential late effects like cognitive deficit or autoimmune manifestations. Collaboration between institutions performing cellular therapy and engagement with patients, clinicians, and statisticians with expertise in PROs are crucial for setting a comprehensive agenda on integration of PROs with CAR-T cell therapy.

  View details for DOI 10.1016/j.bbmt.2018.11.025

  View details for PubMedID 30500439

• Tetraploidy is associated with poor prognosis at diagnosis in multiple myeloma AMERICAN JOURNAL OF HEMATOLOGY Sidana, S., Jevremovic, D., Ketterling, R. P., Tandon, N., Greipp, P. T., Baughn, L. B., Dispenzieri, A., Gertz, M. A., Rajkumar, S., Kumar, S. K. 2019; 94 (5): E117–E120

  View details for DOI 10.1002/ajh.25420

  View details for Web of Science ID 000468303900016

  View details for PubMedID 30680770

• Rapid assessment of hyperdiploidy in plasma cell disorders using a novel multi-parametric flow cytometry method AMERICAN JOURNAL OF HEMATOLOGY Sidana, S., Jevremovic, D., Ketterling, R. P., Tandon, N., Dispenzieri, A., Gertz, M. A., Greipp, P. T., Baughn, L. B., Buadi, F. K., Lacy, M. Q., Morice, W., Hanson, C., Timm, M., Dingli, D., Haynnan, S. R., Gonsalves, W., Kapoor, P., Kyle, R. A., Leung, N., Go, R. S., Lust, J. A., Rajkumar, S., Kumar, S. K. 2019; 94 (4): 424–30

  Abstract

  Trisomies of odd numbered chromosomes are seen in nearly half of patients with multiple myeloma (MM) and typically correlate with a hyperdiploid state and better overall survival (OS). We compared DNA ploidy of monoclonal plasma cells (as a surrogate for the presence of trisomies) assessed simultaneously by PCPRO (plasma cell proliferative index), a novel method that estimates DNA index by multi-parametric flow cytometry to fluorescence in situ hybridization (FISH) in 1703 patients with plasma cell disorders. The distribution of ploidy was hyperdiploid: 759 (45%), diploid 765 (45%), hypodiploid: 71 (4%), tetraploid/near-tetraploid: 108 (6%). FISH identified trisomies in 82% (621/756) of patients with hyperdiploidy by PCPRO and no trisomy by FISH was observed in 88% (730/834) of patients without hyperdiploidy. 95% (795/834) of patients without hyperdiploidy on PCPRO had one or less trisomy by FISH. Sensitivity and specificity of PCPRO for detecting hyperdiploidy was 86% (621/725) and 84% (730/865), respectively. Sensitivity increased to 94% (579/618) for patients with more than one trisomy. Newly diagnosed MM patients with hyperdiploidy on PCPRO (147/275) had better OS compared to nonhyperdiploid patients (median not reached vs 59 months, P = 0.008) and better progression free survival (median: 33 vs 23 months, P = 0.03). Within the hyperdiploidy group, patients with high-hyperdiploidy (DNA index: 1.19-1.50) versus those with low-hyperdiploidy (DNA index: 1.05-1.18) had superior OS (3 year OS of 88% vs 68% P = 0.03). Ploidy assessment by flow cytometry can provide rapid, valuable prognostic information and also reduces the number of copy number FISH probes required and hence the cost of FISH.

  View details for DOI 10.1002/ajh.25391

  View details for Web of Science ID 000460663200018

  View details for PubMedID 30592078

• Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma BLOOD ADVANCES Tandon, N., Sidana, S., Rajkumar, S., Gertz, M. A., Buadi, F. K., Lacy, M. Q., Kapoor, P., Gonsalves, W., Dispenzieri, A., Kourelis, T., Warsame, R., Dingli, D., Fonder, A. L., Hayman, S. R., Hobbs, M. A., Hwa, Y., Kyle, R. A., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Kumar, S. K. 2019; 3 (5): 744–50

  Abstract

  We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and

  View details for DOI 10.1182/bloodadvances.2018022806

  View details for Web of Science ID 000460943400007

  View details for PubMedID 30824418

  View details for PubMedCentralID PMC6418495

• Prognostic Significance of Holter Monitor Findings in Patients With Light Chain Amyloidosis MAYO CLINIC PROCEEDINGS Sidana, S., Tandon, N., Brady, P. A., Grogan, M., Gertz, M. A., Dispenzieri, A., Lin, G., Dingli, D., Buadi, F. K., Lacy, M. Q., Kapoor, P., Gonsalves, W., Muchtar, E., Warsame, R., Kumar, S. K., Kourelis, T. 2019; 94 (3): 455–64

  Abstract

  To evaluate the prognostic impact of Holter findings in patients with light chain amyloidosis.We evaluated 239 patients in whom light chain amyloidosis was diagnosed from January 1, 2010, through December 31, 2015, who underwent 24-hour Holter monitoring.Holter testing was done before stem cell transplant evaluation in 183 of the 239 patients (76.6%) and at diagnosis in 50 (20.9%). Holter findings were nonsustained ventricular tachycardia (NSVT) in 60 patients (25.1%), ventricular couplets in 103 (43.1)%, accelerated idioventricular rhythm in 32 (13.4%), and atrial fibrillation (AF) in 18 (7.5%). Overall survival (OS) at 3 and 6 months after Holter monitoring in patients with AF vs without AF was 78% (95% CI, 54%-91%) vs 96% (95% CI, 92%-98%) (P=.002) and 61% (95% CI, 38%-80%) vs 92% (95% CI, 87%-95%), (P<.001), respectively. In patients with and without NSVT, 3- and 6-month OS after Holter testing was 90% (95% CI, 80%-94%) vs 96% (95% CI, 91%-98%) (P=.12) and 77% (95% CI, 64%-85%) vs 94% (95% CI, 89%-97%) (P<.001), respectively. For patients with and without ventricular couplets, 3- and 6-month OS was 94% (95% CI, 88%-97%) vs 94% (95% CI, 89%-97%) (P=.98) and 84% (95% CI, 75%-89%) vs 94% (95% CI, 89%-97%) (P=.01), respectively. Atrial fibrillation (hazard ratio, 2.5; 95% CI, 1.2-5.0; P=.02) and NSVT (hazard ratio, 2.0; 95% CI, 1.1-3.5; P=.02) were independent predictors for OS after accounting for age and Mayo stage. For patients undergoing routine testing before stem cell transplant, AF (P=.002) and NSVT (P=.02) were associated with inferior OS at 6 months but did not retain statistical significance after adjusting for Mayo stage (P=.10 and P=.54, respectively).Atrial fibrillation and NSVT on 24-hour Holter monitoring are associated with inferior short-term OS outcomes but do not impact peritransplant mortality.

  View details for DOI 10.1016/j.mayocp.2018.08.039

  View details for Web of Science ID 000460059600018

  View details for PubMedID 30718070

• Relapse after complete response in newly diagnosed multiple myeloma: implications of duration of response and patterns of relapse LEUKEMIA Sidana, S., Tandon, N., Dispenzieri, A., Gertz, M. A., Buadi, F. K., Lacy, M. Q., Dingli, D., Fonder, A. L., Hayman, S. R., Hobbs, M. A., Gonsalves, W. I., Warsame, R. M., Kourelis, T., Hwa, Y., Kapoor, P., Kyle, R. A., Leung, N., Go, R. S., Rajkumar, S., Kumar, S. K. 2019; 33 (3): 730–38

  Abstract

  Achieving a complete response (CR) is associated with improved overall survival (OS) in multiple myeloma (MM), but data on duration of CR (DurCR) are limited. We evaluated 351 patients (2004-2016), achieving CR with first-line therapy. Patients with sustained DurCR ≥ 24 months (n = 177) had better OS; 150 vs. 81 months, p < 0.001. DurCR ≥ 24 months remained a significant predictor for OS (HR: 0.3, 95% CI: 0.2-0.5, p < 0.001) after adjusting for age, revised ISS stage, transplant and maintenance therapy. Landmark analysis at 24 months demonstrated similar results, OS: 150 vs. 83 months, p < 0.001. Survival benefit persisted even after loss of CR, with median OS being 89 vs. 56 months (p = 0.005), respectively. Patterns of loss of CR were heterogeneous, with biochemical relapse in 59 (25%); symptomatic relapse in 58 (24%); positive immunofixation/monoclonal protein rise not meeting relapse/progression criteria in 88 (37%) and abnormal free light chain ratio in LC MM in 34 (14%) patients. OS from start of first-line therapy was superior in patients starting second-line treatment for biochemical vs. symptomatic relapse (125 vs. 81 months, p = 0.001). This is likely attributable to underlying disease biology and prevention of end-organ damage by early treatment initiation, as benefit was independent of R-ISS stage.

  View details for DOI 10.1038/s41375-018-0271-1

  View details for Web of Science ID 000460406600015

  View details for PubMedID 30323358

• Primary systemic amyloidosis in patients with Waldenstrom macroglobulinemia LEUKEMIA Zanwar, S., Abeykoon, J. P., Ansell, S. M., Gertz, M. A., Dispenzieri, A., Muchtar, E., Sidana, S., Tandon, N., Rajkumar, S., Dingli, D., Go, R., Lacy, M. Q., Kourelis, T., Witzig, T. E., Inwards, D., Buadi, F., Gonsalves, W., Habermann, T., Johnston, P., Nowakowski, G., Kyle, R. A., Kumar, S., Kapoor, P. 2019; 33 (3): 790–94

  View details for DOI 10.1038/s41375-018-0286-7

  View details for Web of Science ID 000460406600024

  View details for PubMedID 30315235

• A case of ibrutinib-associated aspergillosis presenting with central nervous system, myocardial, pulmonary, intramuscular, and subcutaneous abscesses LEUKEMIA & LYMPHOMA McCarter, S. J., Vijayvargiya, P., Sidana, S., Nault, A. M., Lane, C. E., Lehman, J. S., Wilson, J. W., Parikh, S. A., Nowakowski, G. S., Al-Kali, A. 2019; 60 (2): 559–61

  View details for DOI 10.1080/10428194.2018.1494271

  View details for Web of Science ID 000463555600047

  View details for PubMedID 30070153

• IgM AL amyloidosis: delineating disease biology and outcomes with clinical, genomic and bone marrow morphological features. Leukemia Sidana, S. n., Larson, D. P., Greipp, P. T., He, R. n., McPhail, E. D., Dispenzieri, A. n., Murray, D. L., Dasari, S. n., Ansell, S. M., Muchtar, E. n., Gonsalves, W. I., Kourelis, T. V., Ramirez-Alvarado, M. n., Kapoor, P. n., Rajkumar, S. V., Lacy, M. Q., Buadi, F. K., Leung, N. n., Kyle, R. A., Kumar, S. K., King, R. L., Gertz, M. A. 2019

  Abstract

  This study evaluates newly diagnosed IgM (6%, n = 75/1174) vs. non-IgM light chain amyloidosis patients. IgM amyloid patients had lower light chains (12.5 vs. 22.5 mg/dL; p < 0.001). Heart (56% vs. 73%, p = 0.002) and >1 organ involvement (31% vs. 44%, p = 0.02) was less common in IgM amyloidosis, while soft tissue and peripheral nerve involvement was more common. t(11;14) was less common (27% vs. 50%, p = 0.008) in IgM amyloidosis. Rates of MYD88L265P and CXCR4WHIM mutation in IgM amyloidosis were 58% (29/50) and 17% (8/46). Diagnosis after hematopathology review in IgM amyloidosis was pure plasma cell neoplasm (PPCN) in 23% (16/70), lymphoplasmacytic neoplasm (LPL) in 63% (44/70) patients, and other (14%). LPL vs. PPCN groups had distinct genetic abnormalities: t(11;14): 0% (0/18) vs. 60% (9/15), p < 0.001; MYD88L265P mutation: 84% (27/32) vs. 0% (0/14), p < 0.001; CXCR4 mutation: 29% (8/28) vs. 0% (0/14), p = 0.04. Overall survival was shorter in IgM AL when stratified by Mayo 2012 stage; stage 1/2 (59 vs. 125.9 months, p = 0.003) and stage 3/4 (6.5 vs. 12.9 months, p = 0.075), likely due to lower hematologic response rates (6 months: 39% vs. 59%, p = 0.008). We characterized two subtypes of IgM amyloidosis (LPL/PPCN). This can aid in therapeutic decision-making, with treatment directed at the clonal disease.

  View details for DOI 10.1038/s41375-019-0667-6

  View details for PubMedID 31780812

• Evidence-Based Minireview: Does achieving MRD negativity after initial therapy improve prognosis for high-risk myeloma patients? Hematology. American Society of Hematology. Education Program Sidana, S. n., Manasanch, E. n. 2019; 2019 (1): 142–47

  Abstract

  You are evaluating a 47-year-old man with revised international staging system stage III myeloma who recently underwent an autologous stem cell transplant after receiving 6 cycles of carfilzomib, lenalidomide, and dexamethasone for newly diagnosed disease. Fluorescence in situ hybridization testing at initial presentation also revealed t(4;14). On day 100 evaluation after transplant, he has achieved a stringent complete response. Two-tube, 8-color advanced flow cytometry with a sensitivity of 10-5 shows no minimal residual disease. Whole-body positron emission tomography/computed tomography scan shows resolution of all fluorodeoxyglucose avid uptake seen at diagnosis. The patient asks you how these test results impact his prognosis and whether this overcomes his baseline high risk from t(4;14)?

  View details for DOI 10.1182/hematology.2019000075

  View details for PubMedID 31808853

• CAR T-cell therapy: is it prime time in myeloma? Hematology. American Society of Hematology. Education Program Sidana, S. n., Shah, N. n. 2019; 2019 (1): 260–65

  Abstract

  Chimeric antigen receptor (CAR) T cells have shown promising activity in hematological malignancies and are being studied for the treatment of multiple myeloma, as well. B-cell maturation antigen, which is widely and almost exclusively expressed on plasma cells and B cells, is a promising target. Other targets being evaluated include CD19, CD38, CD138, signaling lymphocyte activation molecule or CS1, light chain, GPRC5D, and NKG2D. Early clinical studies have shown promising response rates in heavily pretreated patients, but relapses have occurred. Cytokine release syndrome and neurotoxicity have been observed in the majority of patients but are mostly grades 1 and 2. Relapse may be mediated by antigen escape and the limited persistence of CAR T cells. CAR T-cell constructs that target multiple antigens/epitopes or constructs with longer persistence due to a higher proportion of memory phenotype T cells may decrease the rates of relapse. Allogeneic CAR T cells that offer "off-the-shelf" options are also being developed. The challenges in integrating CAR T cells in myeloma therapy include disease relapse, adverse effects, cost, and identifying the right patient population. Longer-term data on efficacy and toxicity are needed before CAR T cells are ready for prime time in myeloma.

  View details for DOI 10.1182/hematology.2019000370

  View details for PubMedID 31808895

• CAR T-cell therapy: is it prime time in myeloma? Blood advances Sidana, S. n., Shah, N. n. 2019; 3 (21): 3473–80

  Abstract

  Chimeric antigen receptor (CAR) T cells have shown promising activity in hematological malignancies and are being studied for the treatment of multiple myeloma, as well. B-cell maturation antigen, which is widely and almost exclusively expressed on plasma cells and B cells, is a promising target. Other targets being evaluated include CD19, CD38, CD138, signaling lymphocyte activation molecule or CS1, light chain, GPRC5D, and NKG2D. Early clinical studies have shown promising response rates in heavily pretreated patients, but relapses have occurred. Cytokine release syndrome and neurotoxicity have been observed in the majority of patients but are mostly grades 1 and 2. Relapse may be mediated by antigen escape and the limited persistence of CAR T cells. CAR T-cell constructs that target multiple antigens/epitopes or constructs with longer persistence due to a higher proportion of memory phenotype T cells may decrease the rates of relapse. Allogeneic CAR T cells that offer "off-the-shelf" options are also being developed. The challenges in integrating CAR T cells in myeloma therapy include disease relapse, adverse effects, cost, and identifying the right patient population. Longer-term data on efficacy and toxicity are needed before CAR T cells are ready for prime time in myeloma.

  View details for DOI 10.1182/bloodadvances.2019000370

  View details for PubMedID 31714964

• Should we measure clonal circulating plasma cells in light chain amyloidosis? Oncotarget Sidana, S., Kumar, S. K., Gonsalves, W. I. 2018; 9 (86): 35607–8

  View details for DOI 10.18632/oncotarget.26289

  View details for PubMedID 30479690

• 59-Year-Old Man With Fatigue, Weight Loss, and Hepatomegaly MAYO CLINIC PROCEEDINGS Orme, J. J., Sidana, S., Gonsalves, W. I. 2018; 93 (10): 1525–29

  View details for DOI 10.1016/j.mayocp.2017.12.028

  View details for Web of Science ID 000446070100023

  View details for PubMedID 30104045

• Reply to A. Piccardo et al, E. Hindie et al, MC Kreissl et al, M. Doss, J. Buscombe, R. Fisher, M. Sollini et al, M. Lichtenstein, and M. Tulchinsky et al JOURNAL OF CLINICAL ONCOLOGY Molenaar, R. J., Sidana, S., Radivoyevitch, T., Gerds, A. T., Carraway, H. E., Kalaycio, M., Nazha, A., Adelstein, D. J., Nasr, C., Maciejewski, J. P., Majhail, N. S., Sekeres, M. A., Mukherjee, S. 2018; 36 (18): 1889-+

  View details for DOI 10.1200/JCO.2018.78.4074

  View details for Web of Science ID 000439452300025

  View details for PubMedID 29723096

• Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer JOURNAL OF CLINICAL ONCOLOGY Molenaar, R. J., Sidana, S., Radivoyevitch, T., Advani, A. S., Gerds, A. T., Carraway, H. E., Angelini, D., Kalaycio, M., Nazha, A., Adelstein, D. J., Nasr, C., Maciejewski, J. P., Majhail, N. S., Sekeres, M. A., Mukherjee, S. 2018; 36 (18): 1831-+

  Abstract

  Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

  View details for DOI 10.1200/JCO.2017.75.0232

  View details for Web of Science ID 000439452300010

  View details for PubMedID 29252123

• Prognostic significance of circulating plasma cells by multi-parametric flow cytometry in light chain amyloidosis LEUKEMIA Sidana, S., Tandon, N., Dispenzieri, A., Gertz, M. A., Dingli, D., Jevremovic, D., Morice, W. G., Kapoor, P., Kourelis, T. V., Lacy, M. Q., Hayman, S. R., Buadi, F. K., Leung, N., Go, R. S., Lin, Y., Russell, S. J., Lust, J. A., Zeldenrust, S. R., Warsame, R., Hwa, Y. L., Hobbs, M., Fonder, A., Kyle, R. A., Rajkumar, S., Kumar, S. K., Gonsalves, W. I. 2018; 32 (6): 1421–26

  Abstract

  We evaluated the prognostic impact of clonal circulating plasma cells (cPCs) detected by six-color multi-parametric flow cytometry (MFC) in light chain (AL) amyloidosis at diagnosis. Of the 154 patients who underwent MFC, cPCs were detected in 42% (n = 65) patients. Median number of cPCs was 81 per 150,000 events (range: 6-17,844). High bone marrow plasma cell percentage was an independent predictor of presence of cPCs. Presence of cPCs at diagnosis was associated with inferior overall survival (OS) (90 vs. 98 months, p = 0.003) and inferior progression free survival (PFS) (31 vs. 52 months, p = 0.02). Estimated 1, 2 and 5 year OS in the two groups was: 74, 64 and 57 and 89, 87, and 80%, respectively. Estimated PFS at 1, 2, and 5 years was: 69, 56, and 23% and 80, 74, and 37%, respectively. Furthermore, the presence of cPCs at diagnosis was an independent adverse predictor of OS in multivariable analysis. Achieving a very-good partial response, or better, was able to overcome the adverse impact of cPCs at diagnosis. Patients with cPCs at diagnosis may warrant closer monitoring post-treatment, especially if they do not achieve a deep hematologic response.

  View details for DOI 10.1038/s41375-018-0063-7

  View details for Web of Science ID 000434474100015

  View details for PubMedID 29483709

  View details for PubMedCentralID PMC5992020

• The importance of bone marrow examination in patients with light chain amyloidosis achieving a complete response LEUKEMIA Sidana, S., Tandon, N., Dispenzieri, A., Gertz, M. A., Rajkumar, S., Kumar, S. K. 2018; 32 (5): 1243–46

  View details for DOI 10.1038/s41375-018-0022-3

  View details for Web of Science ID 000431769800020

  View details for PubMedID 29568089

• Impact of prior melphalan exposure on stem cell collection in light chain amyloidosis BONE MARROW TRANSPLANTATION Sidana, S., Tandon, N., Gertz, M. A., Dispenzieri, A., Buadi, F. K., Lacy, M. Q., Dingli, D., Fonder, A. L., Hayman, S. R., Hobbs, M. A., Gonsalves, W. I., Hwa, Y., Kapoor, P., Kyle, R. A., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Zeldenrust, S. R., Rajkumar, S., Hogan, W. J., Kumar, S. K. 2018; 53 (3): 326–33

  Abstract

  Use of melphalan in multiple myeloma was observed to have a deleterious effect on stem cell collection in older studies. There is limited data on the impact of melphalan in light chain (AL) amyloidosis, especially in the plerixafor era. We retrospectively evaluated stem cell mobilization in 610 patients with AL amyloidosis, of which 79 had prior exposure to melphalan, 167 to other chemotherapeutics, while 364 had no chemotherapy exposure. Collection of CD34+ stem cells × 106/kg was lower in the melphalan group. Median total yields in the melphalan, non-melphalan, and no chemotherapy groups were 5.5, 7.7, and 7.8, respectively; p < 0.001. Day-1 yields were 2.7, 3.5, and 4.0 (p = 0.0003), respectively, and median yields per collection were 2.0, 3.3, and 4.0 (p < 0.001), respectively. Similar results were observed in the sub-group analysis after plerixafor was integrated in our collection algorithm (2009). Patients in the melphalan group had higher failure rate of 9% vs. 2% each in the other two groups (p = 0.006). Impact of melphalan was dose-dependent, with cumulative melphalan exposure of >150 mg (median: three cycles) resulting in lower yields. Therefore, duration of melphalan exposure prior to stem cell collection should be limited, ideally, not exceeding more than two cycles of treatment.

  View details for DOI 10.1038/s41409-017-0020-5

  View details for Web of Science ID 000427675200011

  View details for PubMedID 29269795

• Clinical presentation and outcomes in light chain amyloidosis patients with non-evaluable serum free light chains. Leukemia Sidana, S. n., Tandon, N. n., Dispenzieri, A. n., Gertz, M. A., Buadi, F. K., Lacy, M. Q., Dingli, D. n., Fonder, A. L., Hayman, S. R., Hobbs, M. A., Gonsalves, W. I., Hwa, Y. L., Kapoor, P. n., Kyle, R. A., Leung, N. n., Go, R. S., Lust, J. A., Russell, S. J., Zeldenrust, S. R., Rajkumar, S. V., Kumar, S. K. 2018; 32 (3): 729–35

  Abstract

  Hematologic response criteria in light chain (AL) amyloidosis require the difference in involved and uninvolved free light chains (dFLC) to be at least 5 mg/dl. We describe the clinical presentation and outcomes of newly diagnosed amyloidosis patients with dFLC <5 mg/dl (non-evaluable dFLC; 14%, n=165) compared with patients with dFLC ⩾5 mg/dl (evaluable dFLC; 86%, n=975). Patients with non-evaluable dFLC had less cardiac involvement (40% vs 80%, P<0.001), less liver involvement (11% vs 17%, P=0.04) and a trend toward less gastrointestinal involvement (18% vs 25%, P=0.08). However, significantly higher renal involvement (72% vs 56%, P=0.0002) was observed in the non-evaluable dFLC cohort. Differences in treatment patterns were observed, with 51% of treated patients undergoing upfront stem cell transplantation in the non-evaluable cohort compared with 28% in the evaluable dFLC group (P<0.001). Progression-free survival (61 vs 13 months, P<0.001) and overall survival (OS; 101 vs 29 months, P<0.001) were significantly longer in the non-evaluable dFLC cohort. Normalization of involved light chain levels and decrease in dFLC <1 mg/dl (baseline at least 2 mg/dl) were predictive of OS and associated with better dialysis-free survival and may be used for response assessment in patients with non-evaluable FLC levels.

  View details for DOI 10.1038/leu.2017.286

  View details for PubMedID 28919633

• Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL) AMERICAN JOURNAL OF HEMATOLOGY Tandon, N., Sidana, S., Dispenzieri, A., Gertz, M. A., Lacy, M. Q., Dingli, D., Buadi, F. K., Fonder, A. L., Hayman, S. R., Hwa, Y., Hobbs, M. A., Kapoor, P., Gonsalves, W. I., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Kyle, R. A., Rajkumar, S., Kumar, S. K. 2018; 93 (1): 17–22

  Abstract

  Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

  View details for DOI 10.1002/ajh.24919

  View details for Web of Science ID 000417527300011

  View details for PubMedID 28960427

• Risk of developing chronic myeloid neoplasms in well-differentiated thyroid cancer patients treated with radioactive iodine. Leukemia Molenaar, R. J., Pleyer, C. n., Radivoyevitch, T. n., Sidana, S. n., Godley, A. n., Advani, A. S., Gerds, A. T., Carraway, H. E., Kalaycio, M. n., Nazha, A. n., Adelstein, D. J., Nasr, C. n., Angelini, D. n., Maciejewski, J. P., Majhail, N. n., Sekeres, M. A., Mukherjee, S. n. 2018; 32 (4): 952–59

  Abstract

  Exposure to ionizing radiation increases the risk of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), but such risks are not known in well-differentiated thyroid cancer (WDTC) patients treated with radioactive iodine (RAI). A total of 148 215 WDTC patients were identified from Surveillance, Epidemiology and End Results registries between 1973 and 2014, of whom 54% underwent definitive thyroidectomy and 46% received adjuvant RAI. With a median follow-up of 6.6 years, 77 and 66 WDTC patients developed MDS and MPN, respectively. Excess absolute risks for MDS and MPN from RAI treatment when compared to background rates in the US population were 6.6 and 8.1 cases per 100 000 person-years, respectively. Compared to background population rates, relative risks of developing MDS (3.85 (95% confidence interval, 1.7-7.6); P=0.0005) and MPN (3.13 (1.1-6.8); P=0.012) were significantly elevated in the second and third year following adjuvant RAI therapy, but not after thyroidectomy alone. The increased risk was significantly associated with WDTC size ⩾2 cm or regional disease. Development of MDS was associated with shorter median overall survival in WDTC survivors (10.3 vs 22.5 years; P<0.001). These data suggest that RAI treatment for WDTC is associated with increased risk of MDS with short latency and poor survival.

  View details for DOI 10.1038/leu.2017.323

  View details for PubMedID 29104287

• Clinical presentation and outcomes of patients with type 1 monoclonal cryoglobulinemia AMERICAN JOURNAL OF HEMATOLOGY Sidana, S., Rajkumar, S., Dispenzieri, A., Lacy, M. Q., Gertz, M. A., Buadi, F. K., Hayman, S. R., Dingli, D., Kapoor, P., Gonsalves, W. I., Go, R. S., Hwa, Y., Leung, N., Fonder, A. L., Hobbs, M. A., Zeldenrust, S. R., Russell, S. J., Lust, J. A., Kyle, R. A., Kumar, S. K. 2017; 92 (7): 668–73

  Abstract

  We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n = 43, 42%) and ulcers/gangrene (n = 35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n = 24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients. An underlying lymphoproliferative disorder was identified in 94 (92%) subjects; MGUS-39, myeloma-20, lymphoplasmacytic lymphoma-21 and others-14. Treatment was initiated in 73 (72%) patients, primarily for cryoglobulinemia-related symptoms in 57. Treatment regimens consisted of: steroids ± alkylating agents in 29 (40%), novel myeloma therapies in 16 (22%), rituximab with alkylating agents in 12 (16%) and rituximab ± steroids in 11 (15%) patients; 22 patients received plasmapheresis. Six patients underwent autologous stem cell transplant. Cryocrit at treatment initiation, change in cryocrit and time to nadir cryocrit were predictive of symptom improvement. Treatment directed toward the underlying clonal disorder resulted in improvement (n = 47) or stabilization (n = 16) of symptoms in the majority of patients and disappearance of cryoglobulin in over one-half.

  View details for DOI 10.1002/ajh.24745

  View details for Web of Science ID 000405194900016

  View details for PubMedID 28370486

  View details for PubMedCentralID PMC5579826

• Treatment patterns and outcome following initial relapse or refractory disease in patients with systemic light chain amyloidosis AMERICAN JOURNAL OF HEMATOLOGY Tandon, N., Sidana, S., Gertz, M. A., Dispenzieri, A., Lacy, M. Q., Buadi, F. K., Dingli, D., Fonder, A. L., Hobbs, M. A., Hayman, S. R., Gonsalves, W. I., Hwa, Y., Kapoor, P., Kyle, R. A., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Zeldenrust, S. R., Rajkumar, S., Kumar, S. K. 2017; 92 (6): 549–54

  Abstract

  We analyzed the outcomes following initial relapse or refractory disease in systemic light chain amyloidosis (AL) and the impact of type of therapy employed.A total of 1327 patients with AL seen at Mayo Clinic within 90 days of diagnosis, between 2006 and 2015, were reviewed. The study included 366 patients experiencing a documented hematological or organ relapse or refractory disease requiring start of second line therapy. Overall survival (OS) and time to next treatment (TTNT) were calculated from start of second line treatment.The median time to require second line treatment was 16.2 months (1-93) from the start of first line therapy. At relapse, patients received proteasome inhibitors (PI; 45.1%), immunomodulators (IMiD; 22.7%), alkylators (9%), PI and IMiD combination (4.1%), autologous transplant (3.8%), steroids and other therapies (4.9%). Among these, 124 (33.9%) required change or reinstitution of therapy. The median time to require third line treatment was 31 months (95% CI; 24, 40.5) and the median overall survival (OS) was 38.8 months (95% CI; 29.6, 52.6) from the start of second line treatment. Retreatment with same therapy at relapse significantly reduced TTNT (22 m vs 32.3 m; P = .01) as compared to different therapy; but did not have any impact OS (30.8 m vs 51.1 m; P = .5). In conclusion, this study provides important information about outcomes of patients with AL who require second line treatment for relapsed/refractory disease . Treatment with a different therapy at relapse improves time to next therapy but does not impact OS.

  View details for DOI 10.1002/ajh.24723

  View details for Web of Science ID 000400932700029

  View details for PubMedID 28314084

• Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis. PloS one Sidana, S., Narkhede, M., Elson, P., Hastings, D., Faiman, B., Valent, J., Samaras, C., Hamilton, K., Liu, H. K., Smith, M. R., Reu, F. J. 2017; 12 (3): e0172996

  Abstract

  Randomized studies have shown that bortezomib (BTZ) can be given weekly via intravenous (IV) route or twice weekly via subcutaneous (SC) route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial.Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules.Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001) while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15). Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26-4.76, p = 0.008) while the likelihood of not achieving a response (= partial response or better) was comparable (Odds ratio 1.25, 95% CI 0.58-2.71, p = 0.56) for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001).Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.

  View details for DOI 10.1371/journal.pone.0172996

  View details for PubMedID 28278302

  View details for PubMedCentralID PMC5344345

• Revisiting conditioning dose in newly diagnosed light chain amyloidosis undergoing frontline autologous stem cell transplant: impact on response and survival. Bone marrow transplantation Tandon, N. n., Muchtar, E. n., Sidana, S. n., Dispenzieri, A. n., Lacy, M. Q., Dingli, D. n., Buadi, F. K., Hayman, S. R., Chakraborty, R. n., Hogan, W. J., Gonsalves, W. n., Warsame, R. n., Kourelis, T. V., Leung, N. n., Kapoor, P. n., Kumar, S. K., Gertz, M. A. 2017; 52 (8): 1126–32

  Abstract

  Autologous stem cell transplantation (ASCT) is an important treatment modality in light chain (AL) amyloidosis. Use of reduced-dose melphalan conditioning is common, given the associated organ and functional decline. The impact of full-intensity melphalan conditioning (n=314) was compared to reduced-dose conditioning (n=143). Patients in the full-intensity group were younger, with better performance status, fewer involved organs, lower tumor burden and lower Mayo stage. Full-dose conditioning was associated with higher rate of very good partial response or better (79% vs 62%; P<0.001), complete response rate (53% vs 37%; P=0.003) and organ response rate (74% vs 59%; P=0.002) as compared to reduced-dose conditioning. PFS was superior in the full-intensity group compared to the reduced-dose group (4-year PFS 55% vs 31%; P<0.001) as well as a longer overall survival (OS) 4-year OS (86% vs 54%; P<0.001). In addition, the OS and PFS were significantly lower in the reduced-dose group compared to the full-intensity group in Mayo stage III/IV as well as stage I/II. A multivariate analysis confirmed an independent impact for conditioning dose on PFS/OS. This study calls for re-assessment of the use of reduced-dose conditioning in ASCT for AL amyloidosis.

  View details for DOI 10.1038/bmt.2017.68

  View details for PubMedID 28394369

• Predictors of early treatment failure following initial therapy for systemic immunoglobulin light-chain amyloidosis AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS Tandon, N., Sidana, S., Rajkumar, S., Dispenzieri, A., Gertz, M. A., Lacy, M. Q., Kyle, R. A., Buadi, F. K., Dingli, D., Hayman, S. R., Fonder, A. L., Hobbs, M. A., Gonsalves, W. I., Kapoor, P., Hwa, Y., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Zeldenrust, S. R., Kumar, S. K. 2017; 24 (3): 183–88

  Abstract

  We analysed factors predicting early treatment failure (ETF), after first-line therapy for light-chain amyloidosis (AL). AL amyloidosis patients seen at Mayo Clinic within 90 days of diagnosis, from 2006 to 2015, excluding those who died within 3 months of initial therapy, were analysed retrospectively. ETF was defined as progression requiring treatment change or death within 12 (ETF12) or 24 (ETF24) months of first-line treatment. Non-ETF included those with a follow-up of more than 12 or 24 months who had progression beyond 12 or 24 months. A total of 724 patients met the study criteria; 244 (33.7%) had ETF12 and 388 (53.6%) had ETF24. Patients with ETF12 were older (64.1 vs. 62.2 years) with higher prevalence of cardiac (81 vs. 64.1%) and multi-organ involvement (67.2 vs. 45.4%) and higher proportion of patients with t(11; 14) (58.5 vs. 44.3%) or in higher Mayo 2012 stage (58.5 vs. 41.1%).The median follow-up was 5.4 years from start of initial therapy. In multivariate analysis, presence of t(11; 14) and non-incorporation of autologous transplant in initial therapy are significant predictors of ETF12 (p = .01and p = .003) and ETF24 (p = .0001 and p = .005) while Mayo stage is predictive of ETF24 (p = .002), but not ETF12.

  View details for DOI 10.1080/13506129.2017.1351354

  View details for Web of Science ID 000416629600007

  View details for PubMedID 28699793

• Got zinc? An exfoliative rash in a parenteral nutrition-dependent patient. Journal of general internal medicine Sidana, S., Madanat, Y., Pile, J. 2015; 30 (4): 529-30

  View details for DOI 10.1007/s11606-014-3099-z

  View details for PubMedID 25410883

  View details for PubMedCentralID PMC4370997

• Symptomatic and incidental venous thromboembolic disease are both associated with mortality in patients with prostate cancer. PloS one Chaturvedi, S., Sidana, S., Elson, P., Khorana, A. A., McCrae, K. R. 2014; 9 (8): e94048

  Abstract

  The association between malignancy and venous thromboembolic disease (VTE) is well established. The independent impact of VTE, both symptomatic and incidental, on survival in patients with prostate cancer is not known. We conducted a retrospective cohort study to evaluate the effect of VTE of survival in prostate cancer.Data regarding clinical characteristics, treatment and outcomes of 453 consecutive prostate cancer patients were collected. Fisher exact (categorical variables) and t-test (continuous variables) were utilized to test associations with VTE and mortality. Survival was estimated using the Kaplan Meier method. A Cox regression model was used to model the mortality hazard ratio (HR).At diagnosis, 358 (83%) patients had early stage disease, 43 (10%) had locally advanced disease and 32 (7%) had metastatic disease. During the follow up period, 122 (27%) patients died and 41 (9%) developed VTE (33 deep vein thrombosis, 5 pulmonary embolism, and 3 patients with both DVT and PE). Twenty-five VTE events were symptomatic and 16 were incidentally diagnosed on CT scans obtained for other reasons. VTE was associated with increased mortality [HR 6.89 (4.29-11.08), p<0.001] in a multivariable analysis adjusted for cancer stage, performance status, treatments and co-morbidities. There was no difference in survival between patients who had symptomatic and incidental VTE.Venous thromboembolic disease, both symptomatic and incidental, is a predictor of poor survival in patients with prostate cancer, especially those with advanced disease. Further studies are needed to evaluate the benefit of prophylactic and therapeutic anticoagulation in this population.

  View details for DOI 10.1371/journal.pone.0094048

  View details for PubMedID 25126949

  View details for PubMedCentralID PMC4134135

• Prevalence of depression in students of a medical college in New Delhi: A cross-sectional study AUSTRALASIAN MEDICAL JOURNAL Sidana, S., Kishore, J., Ghosh, V., Gulati, D., Jiloha, R. C., Anand, T. 2012; 5 (5): 247–50

  Abstract

  Medical education is associated with various pressures and stresses which can lead to depression. This study was undertaken to discover the prevalence of depression in medical students and various factors contributing to depression.This is a cross-sectional, questionnaire-based study. Using stratified random sampling, 237 students were selected according to year of study. Patient Health Questionnaire (PHQ-9), based on PRIME-MD Today, was used to make a provisional diagnosis of depression.The overall prevalence of provisionally diagnosed depressive and major depressive disorder using PHQ-9 was 21.5% and 7.6%, respectively. Year of study and academic performance of students had a statistically significant association with depression. Other factors, including gender, self-reported past history of depression, family history of psychiatric disorders, type of social support, family structure, number of siblings and education of parents were not found to have any significant association with prevalence of depression in the study. It was also observed that students were reluctant to seek help for depressive symptoms.

  View details for DOI 10.4066/AMJ.2012.750

  View details for Web of Science ID 000218033900001

  View details for PubMedID 22848319

  View details for PubMedCentralID PMC3395288