CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
用于治疗复发/难治性多发性骨髓瘤的新型本地生产抗 BCMA CAR-T 细胞的开发与制备：一项 I 期临床试验结果
英文原题：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.
查看英文原题
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.
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中文摘要
靶向B细胞成熟抗原（BCMA）的CAR-T 细胞治疗对复发和/或难治性（R/R）多发性骨髓瘤（MM）患者显示出显著疗效。HBI0101是一种新型、经优化的第二代抗BCMA CAR-T 疗法，在学术机构环境中开发。
我们对20例接受大量既往治疗的R/R MM患者开展HBI0101 I期剂量递增研究（队列1：1.5×10^8个CAR-T 细胞，n=6；队列2：4.5×10^8个，n=7；队列3：8×10^8个，n=7）。18例患者（90%）报告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。所有队列均未观察到剂量限制性毒性。总缓解率（ORR）、（严格）完全缓解率（CR/sCR）和非常好的部分缓解率分别为75%、50%和25%。缓解率呈剂量依赖性；高剂量队列3的ORR为85%、CR为71%、微小残留病灶阴性率为57%。所有队列中，中位总生存期（OS）为308天（范围25–466天以上）；截至6月27日数据截止时，估计OS为55%。中位无进展生存期为160天，数据截止时6例仍未进展。研究结果显示HBI0101安全性可管理且具有疗效。这些令人鼓舞的数据支持在学术机构环境中分散式生产CAR-T 细胞，以满足不断增长的本地需求并保障供应。试验注册号：NCT04720313。
展开英文摘要原文
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.
论文信息
- 作者
- Asherie N、Kfir-Erenfeld S、Avni B、Assayag M、Dubnikov T、Zalcman N、Lebel E、Zimran E
- 第一作者单位
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem. nathaliea@hadassah.org.il.Israel
- 通讯作者单位
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem. polina@hadassah.org.il.Israel
- 文献类型
- I 期临床试验
- 期刊
- Haematologica2023 Jul 1
- 原文标识
- PubMed 36200421 · DOI 10.3324/haematol.2022.281628
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