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    vhovanky@stanford.edu
    University - Staff Department: Cancer Clinical Trials Office - BMT Position: Cancer Clinical Research Project Manager - Data Quality

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  • Mail Code: 5757

All Publications

  • Enhancing the Safety of Ciltacabtagene Autoleucel in Relapsed Multiple Myeloma (MM):Identification of Potentially Modifiable Risk-Factors Associated with Delayed Neurotoxicity and Non-Relapse Mortality Sidana, S., Reid, B., Dima, D., Peres, L. C., Gaballa, M., Banerjee, R., Pasvolsky, O., Afrough, A., Dillard, C., Ferreri, C., Atrash, S., Varga, C., Portuguese, A. J., Rana, M., Hosoya, H., Mikkilineni, L., Hovanky, V., Zanwar, S. S., Kalariya, N., Mikulski, D., Wagner, C. B., Cahoon, C., Castaneda, O., De Avila, G., Gordillo, C. A., Zolotov, E., Grajales-Cruz, A., Goel, U., Sannareddy, A., Kort, J., Cassano, R., Midha, S., Davis, J., Gonzalez, R., Herr, M. M., Xie, Z., Hassan, H., Purvey, S., Geer, M. J., Green, K., Perna, F., Liu, H., Nishihori, T., Khouri, J., Raza, S., Anwer, F., Bal, S., Nadeem, O., Freeman, C. L., Shune, L., Reshef, R., Shain, K. H., Alsina, M., Baz, R. C., Sborov, D. W., Dahiya, S., Locke, F. L., Miklos, D. B., Voorhees, P. M., Anderson Jr, L. D., Costa, L. J., Biran, N., Kumar, S., Lin, Y., Patel, K., Hansen, D. K. ELSEVIER SCIENCE INC. 2026: S11-S12

    View details for Web of Science ID 001697336900011

  • Minimal Residual Disease Positivity at 3 Months Post Ciltacabtagene Autoleucel Identifies Patients at Risk of Early Relapse Yu, M., Kale, B. J., Jensen, A., Reshef, R., Ferreri, C., Rana, M., Peres, L. C., Varga, C., Galarza-Fortuna, G., Hovanky, V., Sahaf, B., Patil, S., Dima, D., Banerjee, R., Biran, N., Herr, M. M., Gaballa, M., Anderson, L. D., Pasvolsky, O., Freeman, C. L., Grajales-Cruz, A., Afrough, A., Puglianini, O., Purvey, D., McGuirk, J. P., Bhurtel, J., Mikkilineni, L., Sborov, D. W., Miklos, D. B., Patel, K. K., Shune, L., Hansen, D. K., Sidana, S. ELSEVIER SCIENCE INC. 2026

    View details for Web of Science ID 001708751400019

  • Impact of IMWG Frailty and Nutritional Biomarkers on Outcomes in MM Pts Undergoing ASCT Uzun, D., Zhang, A., Austin, R., Yeung, S. B., Kondapally, Y. R., Jensen, A., Hovanky, V., Rana, M., Shizuru, J. A., Arai, S., Rezvani, A. R., Bharadwaj, S., Lowsky, R., Hosoya, H., Miklos, D. B., Muffly, L. S., Sidana, S., Wildes, T. M., Mikkilineni, L. ELSEVIER SCIENCE INC. 2026

    View details for Web of Science ID 001708748200073

  • The Relationship of Baseline and Longitudinal Frailty and Inflammatory Biomarkers with CAR-T Treatment Outcomes in Relapsed Refractory Myeloma Yeung, S. B., Kondapally, Y. R., Uzun, D., Zhang, A., Austin, R., Jensen, A., Hovanky, V., Rana, M., Shizuru, J. A., Arai, S., Rezvani, A. R., Bharadwaj, S., Lowsky, R., Hosoya, H., Miklos, D. B., Muffly, L. S., Sidana, S., Wildes, T. M., Mikkilineni, L. ELSEVIER SCIENCE INC. 2026

    View details for Web of Science ID 001708748200064

  • Impact of Baseline and Dynamic IMWG Simplified Frailty Scores on Outcomes after CAR T-cell and Bispecific Antibody Therapy in Multiple Myeloma Zhang, A., Uzun, D., Yeung, S. B., Kondapally, Y. R., Austin, R., Jensen, A., Hovanky, V., Rana, M., Shizuru, J. A., Arai, S., Rezvani, A. R., Bharadwaj, S., Lowsky, R., Hosoya, H., Miklos, D. B., Muffly, L. S., Sidana, S., Wildes, T. M., Mikkilineni, L. ELSEVIER SCIENCE INC. 2026

    View details for Web of Science ID 001708748200053

  • Safety and efficacy of BCMA directed CAR-T therapy in older patients (Aged > 75) with relapsed or refractory multiple myeloma (RRMM) Velayati, A., Jensen, A., Dima, D., Rana, M., Peres, L., Shune, L., Reid, B., Pasvolsky, O., Portuguese, A., Abdallah, N., Hosoya, H., Mikkilineni, L., Banerjee, R., Cassano, R., Khouri, J., Ferreri, C., Afrough, A., Biran, N., Purvey, S., Fortuna, G., Hovanky, V., Sborov, D., Julian, K., Green, K., Freeman, C., Mcguirk, J., Zolotov, E., Varga, C., Geer, M., Puglianini, O., Goel, U., Gaballa, M., Anwer, F., Raza, S., Dillard, C., Zanwar, S., Dahiya, S., Miklos, D., Davis, J., Herr, M., Alsina, M., Lin, Y., Voorhees, P., Reshef, R., Anderson, L., Patel, K., Hansen, D., Sidana, S. ELSEVIER. 2025: 6375-6376

    View details for DOI 10.1182/blood-2025-6375

    View details for Web of Science ID 001671216100025

  • Non-response to bridging therapy prior to CAR-T is associated with increased toxicity and adverse outcomes in Relapsed/Refractory multiple myeloma (RRMM) Rana, M., Jensen, A., Velayati, A., Hovanky, V., Muffly, L., Sahaf, B., Iberri, D., Liedtke, M., Bharadwaj, S., Kennedy, V., Arai, S., Shiraz, P., Weng, W., Smith, M., Frank, M., Miklos, D., Dahiya, S., Hosoya, H., Mikkilineni, L., Sidana, S. ELSEVIER. 2025: 4586-4587

    View details for DOI 10.1182/blood-2025-4586

    View details for Web of Science ID 001664496300036

  • Real-world outcomes of immune effector cell-associated hemophagocytic syndrome (IEC-HS) following ide-cel and cilta-cel therapy in relapsed/refractory multiple myeloma Lee, J., Jensen, A., Hosoya, H., Afrough, A., Zanwar, S., Pasvolsky, O., Gaballa, M., Dillard, C., Khouri, J., Raza, S., Goel, U., Anwer, F., Hovanky, V., Rana, M., Davis, J., Green, K., Anderson, L., Biran, N., Zolotov, E., Herr, M., Hassan, H., Shune, L., Kort, J., Ferreri, C., Atrash, S., Varga, C., Voorhees, P., Sborov, D., Fortuna, G., Julian, K., Dima, D., Portuguese, A., Banerjee, R., Freeman, C., Salva, K., Cassano, R., Peres, L., Reid, B., Puglianini, O., Grajales-Cruz, A., Jain, M., Patel, K., Locke, F., Frank, M., Lin, Y., Hansen, D., Sidana, S., Shah, N., Mikkilineni, L. ELSEVIER. 2025: 719-720

    View details for DOI 10.1182/blood-2025-719

    View details for Web of Science ID 001659318900020

  • Optimal ferritin threshold to diagnose immune effector cell-associated hemophagocytic syndrome (IEC-HS) following CAR-T therapy in relapsed/refractory multiple myeloma (RRMM) Lee, J., Jensen, A., Hosoya, H., Zanwar, S., Pasvolsky, O., Gaballa, M., Dillard, C., Khouri, J., Raza, S., Goel, U., Anwer, F., Hovanky, V., Rana, M., Davis, J., Green, K., Afrough, A., Anderson, L., Biran, N., Zolotov, E., Herr, M., Hassan, H., Shune, L., Kort, J., Ferreri, C., Atrash, S., Varga, C., Voorhees, P., Sborov, D., Fortuna, G., Julian, K., Dima, D., Banerjee, R., Freeman, C., Portuguese, A., Cassano, R., Locke, F., Salva, K. J., Peres, L., Reid, B., Puglianini, O., Grajales-Cruz, A., Jain, M., Patel, K., Frank, M., Lin, Y., Hansen, D., Sidana, S., Shah, N., Mikkilineni, L. ELSEVIER. 2025: 717-718

    View details for DOI 10.1182/blood-2025-717

    View details for Web of Science ID 001659318900018

  • The real-world safety and efficacy of BCMA-directed chimeric antigen receptor T-cell therapy in systemic AL amyloidosis Rees, M., Cassano, R., Tan, M., Zolotov, E., Sidana, S., Dima, D., Kort, J., Afrough, A., Gaballa, M., Pasvolsky, O., Mikkilineni, L., Khouri, J., Raza, S., Zanwar, S., Ferreri, C., Khan, A., Atrash, S., Portuguese, A., Hovanky, V., Banerjee, R., Freeman, C., Patel, K., Anderson, L., Puglianini, O., Shune, L., Biran, N., Hansen, D., Lin, Y. ELSEVIER. 2025: 2181-2182

    View details for DOI 10.1182/blood-2025-2181

    View details for Web of Science ID 001659513200031

  • Rapid peak CAR-T expansion is associated with delayed neurotoxicity following ciltacabtagene autoleucel in multiple myeloma Hosoya, H., Velayati, A., Dima, D., Jensen, A., Portuguese, A., Hovanky, V., Mikkilineni, L., Peres, L., Homsy, S., Rana, M., Cancilla, J., Ehlinger, Z., Sahaf, B., Latchford, T., Freeman, C., Puglianini, O., Dahiya, S., Locke, F., Miklos, D., Banerjee, R., Hansen, D., Alsina, M., Sidana, S. ELSEVIER. 2025: 96

    View details for DOI 10.1182/blood-2025-96

    View details for Web of Science ID 001659642900047

  • Enhancing the safety of ciltacabtagene autoleucel in relapsed multiple myeloma (MM): Identification of potentially modifiable risk-factors associated with delayed neurotoxicity and non-relapse mortality Sidana, S., Reid, B., Dima, D., Peres, L., Gaballa, M., Banerjee, R., Pasvolsky, O., Afrough, A., Dillard, C., Ferreri, C., Atrash, S., Varga, C., Portuguese, A., Rana, M., Hosoya, H., Mikkilineni, L., Hovanky, V., Zanwar, S., Kalariya, N., Mikulski, D., Wagner, C., Cahoon, C., Puglianini, O., De Avila, G., Gordillo, C., Zolotov, E., Grajales-Cruz, A., Goel, U., Sannareddys, A., Kort, J., Cassano, R., Midha, S., Davis, J., Gonzalez, R., Herrs, M., Xie, Z., Hassan, H., Purvey, S., Geer, M., Green, K., Perna, F., Liu, H., Nishihori, T., Khouri, J., Raza, S., Anwer, F., Bal, S., Nadeem, O., Freeman, C., Shune, L., Reshef, R., Shain, K., Alsina, M., Baz, R., Sborov, D., Dahiya, S., Locke, F., Miklos, D., Voorhees, P., Anderson, L., Costa, L., Biran, N., Kumar, S., Lin, Y., Patel, K., Hansen, D. ELSEVIER. 2025: 1034-1035

    View details for DOI 10.1182/blood-2025-1034

    View details for Web of Science ID 001659353000035

  • Association between cilta-cel dose and efficacy and toxicity outcomes for patients with Relapsed/Refractory multiple myeloma (RRMM): A real-world analysis from the US multiple myeloma immunotherapy consortium Reshef, R., Jensen, A., Gordillo, C., Reid, B., Dima, D., Peres, L., Gaballa, M., Banerjee, R., Pasvolsky, O., Afrough, A., Dillard, C., Ferreri, C., Atrash, S., Varga, C., Portuguese, A., Rana, M., Hosoya, H., Mikkilineni, L., Hovanky, V., Zanwar, S., Kalariya, N., Mikulski, D., Wagner, C., Cahoon, C., Puglianini, O., De Avila, G., Zolotov, E., Bhurtel, E., Grajales-Cruz, A., Goel, U., Sannareddy, A., Kort, J., Cassano, R., Midha, S., Davis, J., Gonzalez, R., Herr, M., Xie, Z., Hassan, H., Purvey, S., Geer, M., Green, K., Perna, F., Liu, H., Nishihori, T., Khouri, J., Raza, S., Anwer, F., Bal, S., Nadeem, O., Freeman, C., Shune, L., Shain, K., Alsina, M., Baz, R., Sborov, D., Dahiya, S., Locke, F., Miklos, D., Voorhees, P., Anderson, L., Costa, L., Biran, N., Kumar, S., Lin, Y., Patel, K., Hansen, D., Sidana, S. ELSEVIER. 2025: 134-135

    View details for DOI 10.1182/blood-2025-134

    View details for Web of Science ID 001660470700035

  • Fludarabine Lymphodepletion Exposure is Associated with Toxicities after Idecabtagene-vicleucel in Relapsed/Refractory Multiple Myeloma: Real-World Experience from the US Myeloma Immunotherapy Consortium. Transplantation and cellular therapy Sweiss, K., Wagner, C., Anto, E., Greene, T., Sun, R., Gonzalez, R., Puglianini, O. C., Freeman, C., Ionescu, F., Patel, K., Ferreri, C., Gaballa, M., Shune, L., McGuirk, J., Sidana, S., Hovanky, V., Khouri, J., Raza, S., Anwer, F., Dima, D., Hashmi, H., Davis, J., Afrough, A., Kaur, G., Anderson, J. L., Forsberg, P., Herr, M., Hansen, D. K., Hakan Kocoglu, M., Sborov, D. 2025

    Abstract

    Idecabtagene vicleucel (ide-cel) is a BCMA-directed CAR-T associated with high response rates in relapsed/refractory multiple myeloma (RRMM), yet responses are not durable and most patients experience toxicities. Fludarabine (Flu) is a key component of lymphodepletion but exhibits significant pharmacokinetic (PK) variability.Given Flu exposure (AUC) predicts outcomes after CD19-directed CAR-T, we hypothesized it would predict outcomes after ide-cel. Our objective was to determine the association between fludarabine AUC and clinical outcomes after standard-of-care (SOC) ide-cel.RRMM patients receiving ide-cel from 10 US Multiple Myeloma Immunotherapy Consortium centers were retrospectively analyzed. A population PK approach using cumulative Flu dose and PK covariates, eGFR and body weight (BW), was used to predict Flu AUC and Cmax and these were tested in univariable and multivariable analysis.285 patients were analyzed, and the median predicted Flu AUC was 19.01 (11.23-41.47) mg * h/L. We observed an association between Flu AUC and Day 90 ORR (OR 2.11; 95% CI 0.99-4.68; p=0.057). Flu AUC was significantly associated with grade ≥1 CRS (p=0.013), and grade ≥1 ICANS (p=0.032), which was consistent with the observed increase in tocilizumab and corticosteroid use in these patients. Flu AUC was also associated with day 60 grade 3/4 thrombocytopenia (p=0.03). A non-statistical but clinically significant increase in the odds of occurrence of day 90 grade 3/4 neutropenia (p=0.058) and infection (p=0.017) was also observed.Predicted Flu exposure is an independent predictor of CAR-T toxicities in this real-world ide-cel-treated population. Validation of these findings with prospective therapeutic drug monitoring is needed to gain further insight into how personalized Flu dosing can mitigate these toxicities after ide-cel.

    View details for DOI 10.1016/j.jtct.2025.08.015

    View details for PubMedID 40972962

  • Rapid Peak CAR-T Expansion is Associated with Delayed Neurotoxicity Following Ciltacabtagene Autoleucel in Multiple Myeloma Hosoya, H., Velayati, A., Dima, D., Jensen, A., Portuguese, A., Hovanky, V., Mikkilineni, L., Peres, L., Homsy, S., Rana, M. S., Cancilla, J., Ehlinger, Z., Sahaf, B., Latchford, T., Freeman, C., Puglianini, O., Dahiya, S., Locke, F., Miklos, D., Banerjee, R., Hansen, D., Alsina, M., Sidana, S. CIG MEDIA GROUP, LP. 2025

    View details for Web of Science ID 001594348400006

  • Immune Reconstitution, Vaccine Protection, and Infectious Complications Following BCMA-Targeted CAR-T Therapy in Relapsed/Refractory Multiple Myeloma Moscvin, M., Goyal, A., Jensen, A., Epstein, D., Hovanky, V., Mikkilineni, L., Bennett, L., Latchford, T., Arai, S., Bharadwaj, S., Frank, M., Dahiya, S., Muffly, L., Miklos, D., Hosoya, H., Sidana, S. CIG MEDIA GROUP, LP. 2025

    View details for Web of Science ID 001605583000075

  • Safety and Efficacy of BCMA directed Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Plasma Cell Leukemia. Blood advances Galarza Fortuna, G. M., Peres, L. C., Nazarenko, E., De Menezes Silva Corraes, A., Hovanky, V., Shune, L., McGuirk, J. P., de Avila, G., Khouri, J., Dima, D., Gaballa, M. R., Dhakal, B., Forsberg, P. A., Godara, A., Afrough, A., Anderson, L. D., Herr, M. M., Davis, J. A., Mann, H., Purvey, S., Clark, W. B., Htut, M. M., Beitinjaneh, A. M., Pereira, D. L., Kocoglu, M., Ferreri, C. J., Atrash, S., Voorhees, P. M., Rossi, A. C., Richard, S., Hashmi, H., Patel, K. K., Sidana, S., Lin, Y., Hansen, D. K., Sborov, D. W. 2025

    Abstract

    Despite significant therapeutic advances in multiple myeloma (MM), outcomes in patients with plasma cell leukemia (PCL) remain dismal. We conducted a multicenter retrospective analysis of patients with PCL treated with the B-cell Maturation Antigen (BCMA)-directed Chimeric Antigen Receptor T-Cell (CAR-T) products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We identified 34 patients, 19 patients received ide-cel and 15 received cilta-cel. With a median follow-up of 11.9 months, the overall median progression free survival (mPFS) was 9.0 months (95% CI 4-15 months) and the median overall survival (mOS) was 13.0 months (95% CI 8-not estimable (NE) months). The 1-year cumulative incidence of progression or death was 72% and the 1-year cumulative incidence of death was 47%. Patients receiving cilta-cel had a longer mPFS (19.0 months vs 6.0 months) and mOS (>23 months (NE) vs 9.0 months) compared to those treated with ide-cel. Similarly, the 1-year cumulative incidence of disease progression or death was 37.5% (95% CI 17.4%-68.5%) with cilta-cel, while all patients treated with ide-cel progressed or died within 12 months of infusion. Rates of hematological and non-hematological toxicities were similar between those patients treated with cilta-cel and ide-cel and consistent with those reported in patients with MM. In this first multicenter study evaluating patients with PCL treated with standard of care CAR-T products, we show that CAR-T is safe, feasible, and associated with improved outcomes compared to historical standards.

    View details for DOI 10.1182/bloodadvances.2025016966

    View details for PubMedID 40875887

  • Cytopenias and infections following ciltacabtagene autoleucel in heavily-pretreated relapsed or refractory multiple myeloma. Haematologica Dima, D., Logue, J. M., Waqar, S. H., Peres, L. C., Colin-Leitzinger, C. M., De Avila, G., Smith, E. C., Skelson, L., Matte, K. L., Blue, B., Hovanky, V. N., Gaballa, M., Pasvolsky, O., Oswald, L. B., Fortuna, G. G., Wagner, C. B., DeJarnette, S., Dillard, C., Perna, F., Mikkilineni, L., Hosoya, H., Freeman, C. L., Shain, K. H., Baz, R. C., Grajales-Cruz, A., Puglianini, O. C., Alsina, M., Locke, F. L., Shune, L. O., Sborov, D. W., Patel, K. K., Sidana, S., Hansen, D. K. 2025

    Abstract

    Ciltacabtagene autoleucel (cilta-cel) was FDA-approved in February 2022 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On CARTITUDE-1 trial, grade ≥3 cytopenias and infections were common. Herein, we sought to characterize cytopenias and infections after cilta-cel infusion in the standard-of-care setting. This multicenter retrospective study included 105 patients who received cilta-cel; 91 reached day-90 and 49 reached day-180 follow-up. Grade ≥3 cytopenia was present among 52% of patients on day-30, and 24% of patients on day-90. Based on the newer immune effector cell-associated hematotoxicity (ICAHT) grading for neutropenia severity, 11 patients (10%) experienced grade ≥3 early ICAHT in the first 30 days, while only 3 (3.3%) experienced grade ≥3 late ICAHT after day-30. On univariate analysis, any grade thrombocytopenia at apheresis was associated with grade ≥3 cytopenia at both days 30 and 90. Granulocyte colony-stimulating factor was administered to 65%, transfusion support to 38%, thrombopoietin agonists to 10%, intravenous immunoglobulin to 52%, and CD34+ stem cell boosts to 9.5% of patients. Infections occurred in 49% of patients and were severe in 32%. Earlier infections in the first 30 days were equally bacterial (42%) and viral (42%). Later infections between days 31-100 and after day 100 were mostly viral (59% and 60%), with only 32% and 12% being grade ≥3 at each time period. On univariate analysis, worse ECOG performance status at lymphodepletion, higher maximum grade of CRS, delayed neurotoxicity, steroid and anakinra use, and lower IgA levels at day 90 were associated with severe infections.

    View details for DOI 10.3324/haematol.2025.287783

    View details for PubMedID 40637727

  • Deciphering response dynamics and treatment resistance from circulating tumor DNA after CAR T-cells in multiple myeloma. Nature communications Hosoya, H., Carleton, M., Tanaka, K., Sworder, B., Syal, S., Sahaf, B., Maltos, A. M., Silva, O., Stehr, H., Hovanky, V., Duran, G., Zhang, T., Liedtke, M., Arai, S., Iberri, D., Miklos, D., Khodadoust, M. S., Sidana, S., Kurtz, D. M. 2025; 16 (1): 1824

    Abstract

    Despite advances in treatments, multiple myeloma (MM) remains an incurable cancer where relapse is common. We developed a circulating tumor DNA (ctDNA) approach in order to characterize tumor genomics, monitor treatment response, and detect early relapse in MM. By sequencing 412 specimens from 64 patients with newly diagnosed or relapsed/refractory disease, we demonstrate the correlation between ctDNA and key clinical biomarkers, as well as patient outcomes. We further extend our approach to simultaneously track CAR-specific cell-free DNA (CAR-cfDNA) in patients undergoing anti-BCMA CAR T-cell (BCMA-CAR) therapy. We demonstrate that ctDNA levels following BCMA-CAR inversely correlate with relative time to progression (TTP), and that measurable residual disease (MRD) quantified by peripheral blood ctDNA (ctDNA-MRD) was concordant with clinical bone marrow MRD. Finally, we show that ctDNA-MRD can anticipate clinical relapse and identify the emergence of genomically-defined therapy-resistant clones. These findings suggest multiple clinical uses of ctDNA for MM in molecular characterization and disease surveillance.

    View details for DOI 10.1038/s41467-025-56486-6

    View details for PubMedID 39979252

    View details for PubMedCentralID 3783001

  • Anti-BCMA CAR T-Cell Expansion and Its Association with Response and Toxicity in Multiple Myeloma Hosoya, H., Jensen, A., Hovanky, V., Homsy, S., Cancilla, J. E., Patil, S., Kennedy, V. E., Bharadwaj, S., Smith, M., Shiraz, P., Frank, M. J., Dahiya, S., Arai, S., Weng, W., Muffly, L., Sahaf, B., Mackall, C. L., Miklos, D. B., Mikkilineni, L., Sidana, S. ELSEVIER. 2024: 2006-2007

    View details for DOI 10.1182/blood-2024-211128

    View details for Web of Science ID 001412856700030

  • Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma. Blood Sidana, S., Patel, K. K., Peres, L. C., Bansal, R., Kocoglu, M. H., Shune, L., Atrash, S., Smith, K., Midha, S., Ferreri, C. J., Dhakal, B., Dima, D., Costello, P., Wagner, C., Reshef, R., Hosoya, H., Mikkilineni, L., Atanackovic, D., Chhabra, S., Parrondo, R. D., Nadeem, O., Mann, H., Kalariya, N., Hovanky, V., DeAvila, G., Freeman, C. L., Locke, F. L., Alsina, M., Wong, S., Herr, M. M., Htut, M., McGuirk, J. P., Sborov, D. W., Khouri, J., Martin, T., Janakiram, M., Lin, Y., Hansen, D. K. 2024

    Abstract

    Ciltacabtagene autoleucel (cilta-cel) CAR-T therapy was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 3/1/2022-12/31/2022 at 16 US academic medical centers were included. RESULTS: 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel. Of leukapheresed patients, 56% would not have met CARTITUDE-1 trial eligibility criteria. Manufacturing failure rates at first attempt and overall were 6% and 1%, respectively. Median prior lines of therapy were 6. In treated patients (N=236), cytokine release syndrome was seen in 75% (>= grade 3: 5%), immune effector cell-associated neurotoxicity syndrome in 14% (>= grade 3: 4%), and delayed neurotoxicity in 10%. Best overall and >= CR rates were as follows: infused patients (N=236): 89% and 70%; patients receiving conforming CAR-T product (N=191) 94% and 74%; conforming CAR-T product with fludarabine/cyclophosphamide lymphodepletion (N=152): 95% and 76%, respectively. Non-relapse mortality was 10%, most commonly from infection. After median follow-up of 13 months from CAR-T, median progression-free survival (PFS) was not reached, with 12- month estimate being 68% (95% CI: 62-74%). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior BCMA-TT (p=0.08). Second primary malignancies (SPMs) excluding non-melanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard of care cilta-cel in RRMM despite more than half the patients not meeting CARTITUDE-1 eligibility criteria.

    View details for DOI 10.1182/blood.2024025945

    View details for PubMedID 39365257

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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