Deepu Madduri

All Publications

• Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. Nature medicine Lin, Y., Raje, N. S., Berdeja, J. G., Siegel, D. S., Jagannath, S., Madduri, D., Liedtke, M., Rosenblatt, J., Maus, M. V., Massaro, M., Petrocca, F., Yeri, A., Finney, O., Caia, A., Yang, Z., Martin, N., Campbell, T. B., Rytlewski, J., Fuller, J., Hege, K., Munshi, N. C., Kochenderfer, J. N. 2023

  Abstract

  Idecabtagene vicleucel (ide-cel) is a B-cell-maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy. We performed a post hoc analysis of a single-arm phase 1 multicenter study in relapsed/refractory multiple myeloma (CRB-401) (n = 62; median follow-up, 18.1 months). The primary endpoint was safety outcomes, and secondary endpoints included overall response rate (ORR), complete response (CR) and very good partial response (VGPR). The study met its primary endpoint with low rates of grade 3/grade 4 cytokine release syndrome (6.5%) and neurotoxicity (1.6%). ORR was 75.8%; 64.5% achieved VGPR or better and 38.7% achieved CR or stringent CR. Among exploratory endpoints, median duration of response, progression-free survival (PFS) and overall survival were 10.3, 8.8 and 34.2 months, respectively, and ide-cel expansion in blood and bone marrow correlated with clinical efficacy and postinfusion reduction of soluble BCMA. Patients with PFS ≥ 18 months had more naive and less exhausted T cells in apheresis material and improved functional T cell phenotype in the drug product compared with those with less durable responses. These results confirm ide-cel safety, tolerability and efficacy and describe T cell qualities that correlate with durable response. Clinicaltrials.gov identifier : NCT02658929 .

  View details for DOI 10.1038/s41591-023-02496-0

  View details for PubMedID 37592106

  View details for PubMedCentralID 8213772

• Efficacy and Safety of Ciltacabtagene Autoleucel in Patients With Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 Subgroup Analysis Jakubowiak, A., Usmani, S. Z., Berdeja, J. G., Agha, M., Cohen, A. D., Hari, P., Schecter, J. M., Madduri, D., Yeh, T., Olyslager, Y., Banerjee, A., Jackson, C. C., Allred, A., Zudaire, E., Deraedt, W., Zhou, C., Geng, D., Pacaud, L., Lin, Y., Martin, T., Jagannath, S. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-146069

  View details for Web of Science ID 000736413908062

• Updated Results from CARTITUDE-1: Phase 1b/2Study of Ciltacabtagene Autoleucel, a B-Cell Maturation AntigenDirected Chimeric Antigen Receptor T Cell Therapy, in Patients With Relapsed/Refractory Multiple Myeloma Martin, T., Usmani, S. Z., Berdeja, J. G., Jakubowiak, A., Agha, M., Cohen, A. D., Hari, P., Avigan, D., Deol, A., Htut, M., Lesokhin, A., Munshi, N. C., O'Donnell, E., Stewart, A., Schecter, J. M., Goldberg, J. D., Jackson, C. C., Yeh, T., Banerjee, A., Allred, A., Zudaire, E., Deraedt, W., Madduri, D., Olyslager, Y., Zhou, C., Pacaud, L., Lin, Y., Jagannath, S. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-146060

  View details for Web of Science ID 000736398802090

• Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study (vol 398, pg 314, 2021) LANCET Berdeja, J. G., Madduri, D., Usmani, S. Z. 2021; 398 (10307): 1216

  View details for Web of Science ID 000704393000019

• Incidence, mitigation, and management of neurologic adverse events in CARTITUDE-2, a phase 2 study of ciltacabtagene autoleucel (cilta-cel) in patients with Multiple Myeloma Einsele, H., Parekh, S., Madduri, D., Santomasso, B., Gallego Perez-Larraya, J., van de Donk, N. J., Arnulf, B., Mateos, M., De Braganca, K. C., Varsos, H., Carrasco-Alfonso, M. J., Akram, M., Lendvai, N., Jackson, C. C., Olyslager, Y., Zudaire, E., Li, C., Geng, D., Jakubowiak, A., Cohen, A. CIG MEDIA GROUP, LP. 2021: S120-S121

  View details for Web of Science ID 000717640800209

• Efficacy and safety of ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in patients with progressive multiple myeloma after 1-3 prior lines of therapy: Initial results from CARTITUDE-2 Cohen, A., Agha, M., Madduri, D., Cohen, Y., Delforge, M., Hillengass, J., Goldschmidt, H., Weisel, K., Raab, M., Scheid, C., Schecter, J. M., De Braganca, K. C., Varsos, H., Wang, L., Vogel, M., Carrasco-Alfonso, M., Akram, M., Wu, X., Nesheiwat, T., Einsele, H. CIG MEDIA GROUP, LP. 2021: S15

  View details for Web of Science ID 000717640800024

• Updated results from CARTITUDE-1: Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T (CAR-T) cell therapy, in relapsed/refractory multiple myeloma (RRMM) Jagannath, S., Berdeja, J. G., Jakubowiak, A., Agha, M., Cohen, A., Madduri, D., Hari, P., Yeh, T., Olyslager, Y., Banerjee, A., Jackson, C. C., Allred, A., Zudaire, E., Deraedt, W., Wu, X., Pacaud, L., Akram, M., Lin, Y., Martin, T., Usmani, S. Z. CIG MEDIA GROUP, LP. 2021: S15-S16

  View details for Web of Science ID 000717640800025

• Incidence, Mitigation, and Management of Neurologic Adverse Events in the CARTITUDE-2 Study of Patients with Multiple Myeloma Treated with Ciltacabtagene Autoleucel (Cilta-Cel) Jakubowiak, A., Parekh, S., Madduri, D., Santomasso, B., Gallego Perez-Larraya, J., van de Donk, N. J., Arnulf, B., Mateos, M., De Braganca, K. C., Varsos, H., Carrasco-Alfonso, M. J., Akram, M., Lendvai, N., Jackson, C. C., Olyslager, Y., Zudaire, E., Li, C., Geng, D., Einsele, H., Cohen, A. CIG MEDIA GROUP, LP. 2021: S421-S422

  View details for Web of Science ID 000691910500383

• Ciltacabtagene autoleucel, a B-cell maturation antigendirected chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study LANCET Berdeja, J. G., Madduri, D., Usmani, S. Z., Jakubowiak, A., Agha, M., Cohen, A. D., Stewart, A., Hari, P., Htut, M., Lesokhin, A., Deol, A., Munshi, N. C., O'Donnell, E., Avigan, D., Singh, I., Zudaire, E., Yeh, T., Allred, A. J., Olyslager, Y., Banerjee, A., Jackson, C. C., Goldberg, J. D., Schecter, J. M., Deraedt, W., Zhuang, S., Infante, J., Geng, D., Wu, X., Carrasco-Alfonso, M. J., Akram, M., Hossain, F., Rizvi, S., Fan, F., Lin, Y., Martin, T., Jagannath, S. 2021; 398 (10297): 314-324

  Abstract

  CARTITUDE-1 aimed to assess the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma with poor prognosis.This single-arm, open-label, phase 1b/2 study done at 16 centres in the USA enrolled patients aged 18 years or older with a diagnosis of multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0·75 × 106 CAR-positive viable T cells per kg) was administered 5-7 days after start of lymphodepletion. The primary endpoints were safety and confirmation of the recommended phase 2 dose (phase 1b), and overall response rate (phase 2) in all patients who received treatment. Key secondary endpoints were duration of response and progression-free survival. This trial is registered with ClinicalTrials.gov, NCT03548207.Between July 16, 2018, and Oct 7, 2019, 113 patients were enrolled. 97 patients (29 in phase 1b and 68 in phase 2) received a cilta-cel infusion at the recommended phase 2 dose of 0·75 × 106 CAR-positive viable T cells per kg. As of the Sept 1, 2020 clinical cutoff, median follow-up was 12·4 months (IQR 10·6-15·2). 97 patients with a median of six previous therapies received cilta-cel. Overall response rate was 97% (95% CI 91·2-99·4; 94 of 97 patients); 65 (67%) achieved stringent complete response; time to first response was 1 month (IQR 0·9-1·0). Responses deepened over time. Median duration of response was not reached (95% CI 15·9-not estimable), neither was progression-free survival (16·8-not estimable). The 12-month progression-free rate was 77% (95% CI 66·0-84·3) and overall survival rate was 89% (80·2-93·5). Haematological adverse events were common; grade 3-4 haematological adverse events were neutropenia (92 [95%] of 97 patients), anaemia (66 [68%]), leukopenia (59 [61%]), thrombocytopenia (58 [60%]), and lymphopenia (48 [50%]). Cytokine release syndrome occurred in 92 (95%) of 97 patients (4% were grade 3 or 4); with median time to onset of 7·0 days (IQR 5-8) and median duration of 4·0 days (IQR 3-6). Cytokine release syndrome resolved in all except one with grade 5 cytokine release syndrome and haemophagocytic lymphohistiocytosis. CAR T-cell neurotoxicity occurred in 20 (21%) patients (9% were grade 3 or 4). 14 deaths occurred in the study; six due to treatment-related adverse events, five due to progressive disease, and three due to treatment-unrelated adverse events.A single cilta-cel infusion at the target dose of 0·75 × 106 CAR-positive viable T cells per kg led to early, deep, and durable responses in heavily pretreated patients with multiple myeloma with a manageable safety profile. The data from this study formed the basis for recent regulatory submissions.Janssen Research & Development and Legend Biotech.

  View details for DOI 10.1016/S0140-6736(21)00933-8

  View details for Web of Science ID 000675849600023

  View details for PubMedID 34175021

• Incidence, mitigation, and management of neurologic adverse events in patients with multiple myeloma (MM) treated with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-2. Einsele, H., Parekh, S. S., Madduri, D., Santomasso, B., De larraya, J., van de Donk, N. J., Arnulf, B., Mateos, M., De Braganca, K. C., Varsos, H., Carrasco-Alfonso, M., Akram, M., Lendvai, N., Jackson, C., Olyslager, Y., Zudaire, E., Li, C., Geng, D., Jakubowiak, A. J., Cohen, A. D. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.8028

  View details for Web of Science ID 000708120604191

• Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed/refractory multiple myeloma (R/R MM): Updated results from CARTITUDE-1. Usmani, S., Berdeja, J. G., Madduri, D., Jakubowiak, A. J., Agha, M. E., Cohen, A. D., Hari, P., Yeh, T., Olyslager, Y., Banerjee, A., Jackson, C., Allred, A., Zudaire, E., Deraedt, W., Wu, X., Carrasco-Alfonso, M., Akram, M., Lin, Y., Martin, T. G., Jagannath, S. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.8005

  View details for Web of Science ID 000708120604168

• CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma (MM) after one to three prior lines of therapy. Agha, M. E., Cohen, A. D., Madduri, D., Cohen, Y. C., Delforge, M., Hillengass, J., Goldschmidt, H., Weisel, K., Raab, M., Scheid, C., Schecter, J., De Braganca, K. C., Varsos, H., Wang, L., Vogel, M., Carrasco-Alfonso, M., Akram, M., Wu, X., Nesheiwat, T., Einsele, H. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.8013

  View details for Web of Science ID 000708120604176

• CARTITUDE-1: Phase 1b/2 study of ciltacabtagene autoleucel in relapsed/Refractory multiple myeloma Madduri, D., Berdeja, J., Usmani, S., Jakubowiak, A., Agha, M., Cohen, A., Stewart, A., Hari, P., Htut, M., O'Donnell, E., Munshi, N., Avigan, D., Deol, A., Lesokhin, A., Singh, I., Zudaire, E., Yeh, T., Allred, A., Olyslager, Y., Banerjee, A., Goldberg, J., Schecter, J., Jackson, C., Deraedt, W., Zhuang, S., Infante, J., Geng, D., Wu, X., Carrasco-Alfonso, M., Akram, M., Hossain, F., Rizvi, S., Fan, F., Jagannath, S., Lin, Y., Martin, T. WILEY. 2021: 16-17

  View details for Web of Science ID 000645412200017

• SAFETY AND MANAGEMENT OF ADVERSE EVENTS WITH CILTACABTAGENE AUTOLEUCEL, A CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL RESULTS FROM CARTITUDE-1 Florendo, E., Wilmoth, J., Romanov, V., Garrett, A., Martin, T., Madduri, D. ONCOLOGY NURSING SOC. 2021

  View details for Web of Science ID 000620349200263

• Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma NEW ENGLAND JOURNAL OF MEDICINE Raje, N., Berdeja, J., Lin, Y., Siegel, D., Jagannath, S., Madduri, D., Liedtke, M., Rosenblatt, J., Maus, M. V., Turka, A., Lam, L., Morgan, R. A., Friedman, K., Massaro, M., Wang, J., Russotti, G., Yang, Z., Campbell, T., Hege, K., Petrocca, F., Quigley, M., Munshi, N., Kochenderfer, J. N. 2019; 380 (18): 1726–37

  View details for DOI 10.1056/NEJMoa1817226

  View details for Web of Science ID 000467767800008

• Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. The New England journal of medicine Raje, N. n., Berdeja, J. n., Lin, Y. n., Siegel, D. n., Jagannath, S. n., Madduri, D. n., Liedtke, M. n., Rosenblatt, J. n., Maus, M. V., Turka, A. n., Lam, L. P., Morgan, R. A., Friedman, K. n., Massaro, M. n., Wang, J. n., Russotti, G. n., Yang, Z. n., Campbell, T. n., Hege, K. n., Petrocca, F. n., Quigley, M. T., Munshi, N. n., Kochenderfer, J. N. 2019; 380 (18): 1726–37

  Abstract

  Preclinical studies suggest that bb2121, a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA), has potential for the treatment of multiple myeloma.In this phase 1 study involving patients with relapsed or refractory multiple myeloma, we administered bb2121 as a single infusion at doses of 50×106, 150×106, 450×106, or 800×106 CAR-positive (CAR+) T cells in the dose-escalation phase and 150×106 to 450×106 CAR+ T cells in the expansion phase. Patients had received at least three previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or were refractory to both drug classes. The primary end point was safety.Results for the first 33 consecutive patients who received a bb2121 infusion are reported. The data-cutoff date was 6.2 months after the last infusion date. Hematologic toxic effects were the most common events of grade 3 or higher, including neutropenia (in 85% of the patients), leukopenia (in 58%), anemia (in 45%), and thrombocytopenia (in 45%). A total of 25 patients (76%) had cytokine release syndrome, which was of grade 1 or 2 in 23 patients (70%) and grade 3 in 2 patients (6%). Neurologic toxic effects occurred in 14 patients (42%) and were of grade 1 or 2 in 13 patients (39%). One patient (3%) had a reversible grade 4 neurologic toxic effect. The objective response rate was 85%, including 15 patients (45%) with complete responses. Six of the 15 patients who had a complete response have had a relapse. The median progression-free survival was 11.8 months (95% confidence interval, 6.2 to 17.8). All 16 patients who had a response (partial response or better) and who could be evaluated for minimal residual disease (MRD) had MRD-negative status (≤10-4 nucleated cells). CAR T-cell expansion was associated with responses, and CAR T cells persisted up to 1 year after the infusion.We report the initial toxicity profile of a BCMA-directed cellular immunotherapy for patients with relapsed or refractory multiple myeloma. Antitumor activity was documented. (Funded by Bluebird Bio and Celgene; CRB-401 ClinicalTrials.gov number, NCT02658929.).

  View details for PubMedID 31042825

• bb2121 anti-BCMA CAR T-cell therapy in patients with relapsed/refractory multiple myeloma: Updated results from a multicenter phase I study. Raje, N. S., Berdeja, J. G., Lin, Y., Munshi, N. C., Samuel, D., Siegel, D., Liedtke, M., Jagannath, S., Madduri, D., Rosenblatt, J., Maus, M., Turka, A., Lam, L., Morgan, R. A., Quigley, T., Massaro, M., Hege, K., Petrocca, F., Kochenderfer, J. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.8007

  View details for Web of Science ID 000442916003054

• Association of high baseline ferritin with tocilizumab administration for CRS in relapsed/refractory multiple myeloma patients treated with bb2121 anti-BCMA CAR T cells Berdeja, J. G., Lin, Y., Kochenderfer, J., Raje, N. S., Munshi, N. C., Siegel, D., Liedtke, M., Madduri, D., Rosenblatt, J., Maus, M., Turka, A., Lam, L., Hege, K., Campbell, T., Massaro, M., Petrocca, F., Jagannath, S. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.e15062

  View details for Web of Science ID 000442916004667

• Early MRD negativity to predict deepening myeloma response in relapsed/refractory multiple myeloma (RRMM) patients treated with bb2121 anti-BCMA CAR T cells. Munshi, N. C., Berdeja, J. G., Lin, Y., Kochenderfer, J., Raje, N. S., Liedtke, M., Jagannath, S., Madduri, D., Rosenblatt, J., Maus, M., Turka, A., Lam, L., Hege, K., Campbell, T., Massaro, M., Petrocca, F., Siegel, D. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.8024

  View details for Web of Science ID 000442916003071