Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem.
Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem.
Haematologica. 2023 Jul 1;108(7):1827-1839. doi: 10.3324/haematol.2022.281628.
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.
抗 B 细胞成熟抗原 (BCMA) 嵌合抗原受体 T 细胞 (CAR T) 疗法在复发和/或难治性 (R/R) 多发性骨髓瘤 (MM) 患者中显示出显著疗效。HBI0101 是一种新型第二代优化的抗 BCMA CAR T 细胞疗法，是在学术环境中开发的。我们在 20 名接受过多重预处理的 R/R MM 患者中进行了 HBI0101 的 I 期剂量递增研究（队列 1：150x106 CAR T 细胞，n=6；队列 2：450x106 CAR T 细胞，n=7；队列 3：800x106 CAR T 细胞，n=7）。18 名患者（90%）报告了 1-2 级细胞因子释放综合征 (CRS)。未观察到 3-4 级 CRS 或任何级别神经毒性。任何队列均未观察到剂量限制毒性。总缓解率 (ORR)、（严格）完全缓解 (CR/sCR) 和非常好的部分缓解率分别为 75%、50%和 25%。高剂量队列 3 的缓解率呈剂量依赖性，ORR 为 85%，CR 为 71%，微小残留病阴性率为 57%。在所有队列中，中位总生存期 (OS) 为 308 天（范围 25-466+），截至 2023 年 6 月 27 日（数据截止），估计 OS 为 55%。中位无进展生存期为 160 天，数据截止时仍有 6 名患者无进展。我们的发现表明 HBI0101 具有可管理的安全性和疗效。这些令人鼓舞的数据支持在学术环境中分散 CAR T 生产，以确保有足够的 CAR T 供应来满足不断增长的当地需求。Clinicaltrials.gov NCT04720313。
