Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM). HBI0101, a novel second generation optimized anti-BCMA CAR T-cell therapy, was developed in an academic setting. We conducted a phase I dose-escalation study of HBI0101 (cohort 1: 150x106 CAR T cells, n=6; cohort 2: 450x106 CAR T cells, n=7; cohort 3: 800x106 CAR T cells, n=7) in 20 heavily pre-treated R/R MM patients. Grade 1-2 cytokine release syndrome (CRS) was reported in 18 patients (90%). Neither grade 3-4 CRS nor neurotoxicity of any grade were observed. No dose-limiting toxicities were observed in any cohort. The overall response rate (ORR), (stringent) complete response (CR/sCR), and very good partial response rates were 75%, 50%, and 25%, respectively. Response rates were dose-dependent with 85% ORR, 71% CR, and 57% minimal residual disease negativity in the high-dose cohort 3. Across all cohorts, the median overall survival (OS) was 308 days (range 25-466+), with an estimated OS of 55% as of June 27th (data cut-off). The median progression-free survival was 160 days, with 6 subjects remaining progression free at the time of data cut-off. Our findings demonstrate the manageable safety profile and efficacy of HBI0101. These encouraging data support the decentralization of CAR T production in an academic setting, ensuring sufficient CAR T supply to satisfy the increasing local demand. Clinicaltrials.gov NCT04720313.
Bibliographical noteFunding Information:
We would like to thank the patients and their families for participating in the study. We would also like to express our gratitude to the management of Hadassah Medical Center for their ongoing support and their deep commitment to innovation. We also thank the staff in the clinical units for patient care, Mrs. Avigail Avraham from the apheresis unit, Mrs. Nassreen Hussein for cell manufacturing, and Mrs. Gili Gruzman for QC testing and patient follow-up. We are extremely grateful for the generous support for this clinical research under the leadership of Prof. Polina Stepensky, by The Manfred Steinfeld Family and The Estate of Allan Habelson. We gratefully acknowledge the support of the Amyloidosis Patient Association of Israel. CJC is supported by the Adelis Foundation and the Israel Science Foundation (646/20).
CJC is supported by the Adelis Foundation and the Israel Science Foundation (646/20).
©2023 Ferrata Storti Foundation Published under a CC BY-NC license.