Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial
Nathalie Asherie,
Shlomit Kfir-Erenfeld,
Batia Avni,
Miri Assayag,
Tatyana Dubnikov,
Nomi Zalcman,
Eyal Lebel,
Eran Zimran,
Adir Shaulov,
Marjorie Pick,
Yael Cohen,
Irit Avivi,
Cyrille Cohen,
Moshe E. Gatt,
Sigal Grisariu,
Polina Stepensky
Affiliations
Nathalie Asherie
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Shlomit Kfir-Erenfeld
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Batia Avni
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Miri Assayag
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Tatyana Dubnikov
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Nomi Zalcman
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Eyal Lebel
Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Eran Zimran
Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Adir Shaulov
Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Marjorie Pick
Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Yael Cohen
Department of Hematology, Aviv Medical Center, Sackler faculty of medicine, Aviv University
Irit Avivi
Department of Hematology, Aviv Medical Center, Sackler faculty of medicine, Aviv University
Cyrille Cohen
Laboratory of Tumor Immunology and Immunotherapy, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900-02, Israel
Moshe E. Gatt
Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Sigal Grisariu
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
Polina Stepensky
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
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.
