Journal Article

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma

Zhang, Hui, Geng, Yan, Wang, Xu-Geng, Gu, Liu-Fang, Zhang, Wang-Gang, Yang, Nan, Liu, Jie, Xu, Yan, Wang, Jian-Li, He, Ai-Li, Zhao, Wan-Hong, Shen, Ying, Zhang, Ru, Zhang, Peng-Yu, Wang, Fang-Xia, Lei, Bo, He, Qian, Zhang, Rui-Li, Wang, Bai-Yan, Wei, Li-Li, Zhang, Yi-Lin, Li, Zhen-Zhen, Cao, Xing-Mei, Zhuang, Qiu-Chuan, Yang, Yun, Bai, Ju, Fan, Xiao-Hu, Chen, Yin-Xia, Li, Zong-Fang

2018

Overview

Background Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). Methods This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m 2 . LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10 6 cells/kg [range, 0.07 to 2.1 × 10 6 ]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. Results At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. Conclusions LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. Trial registration ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adolescent / Adult / Aged / Aged, 80 and over / Antigen receptors, T cell / Antigens / Aphasia / Aspartate aminotransferase / B-Cell Maturation Antigen - metabolism / BCMA / Blood cancer / Cancer / Cancer Research / CAR T / Care and treatment / Cell therapy / Cellular therapy / Chimeric antigen receptor / Chimeric antigen receptors / Cyclophosphamide / Cytokines / Epitopes / Female / Genetic aspects / Health risk assessment / Hematology / Humans / Leukemia / Leukopenia / Lymphocytes / Lymphocytes B / Lymphocytes T / Lymphoma / Male / Medical prognosis / Medicine / Medicine & Public Health / Middle Aged / Minimal residual disease / Multiple myeloma / Multiple Myeloma - drug therapy / Multiple Myeloma - pathology / Neurotoxicity / Oncology / Patients / Physiological aspects / Receptors / Receptors, Chimeric Antigen - metabolism / Refractory / Relapsed / Remission Induction / Safety / Studies / T cell antigen receptors / T cells / Thrombocytopenia / Working groups / Young Adult