A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma
A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma
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新型全人 BCMA 靶向 CAR (CT103A) 在复发/难治性多发性骨髓瘤患者中的 I 期研究
DOI：
10.1182/blood.2020008936
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发表时间：
2021-05-27
期刊：
影响因子：
20.3
通讯作者：
Zhou, Jianfeng
中科院分区：
文献类型：
--
作者：
Wang, Di;Wang, Jue;Zhou, Jianfeng
B细胞成熟抗原（BCMA）特异性嵌合抗原受体（CAR）T细胞疗法已显示出对复发性/难治性多发性骨髓瘤（RRMM）的疗效。由于非人源性抗原靶向结构域可能限制临床疗效，我们开发了完全人BCMA特异性CAR CT 103 A，并在1期试验中报告了其安全性和疗效。入组了18例连续RRMM患者，包括4例既往暴露于鼠BCMA CAR的患者。CT 103 A在剂量递增阶段以1、3和6 × 10（6）CAR阳性T细胞/kg给药，在扩增队列中以1 × 10（6）CAR阳性T细胞/kg给药。总有效率为100%，其中72.2%的患者达到完全缓解或严格完全缓解。对于4名鼠BCMA CAR暴露患者，3名实现严格的完全应答，1名实现非常好的部分应答。1年时，所有队列的无进展生存率为58.3%，无髓外骨髓瘤患者的无进展生存率为79.1%。血液学毒性是最常见的不良事件; 70.6%的患者发生1级或2级细胞因子释放综合征。未观察到免疫效应细胞相关神经毒性综合征。截至截止日期，77.8%的患者可检测到CAR转基因。中位CAR转基因持续时间为307.5天。仅1例患者的抗药抗体呈阳性。总的来说，CT 103 A在RRMM患者中是安全的和高活性的，可以开发为RRMM的有希望的治疗方法。从先前的鼠BCMA CAR T细胞疗法复发的患者仍然可以从CT 103 A中受益。
B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies have shown efficacy in relapsed/refractory multiple myeloma (RRMM). Because the non-human originated antigen-targeting domain may limit clinical efficacy, we developed a fully human BCMAspecific CAR, CT103A, and report its safety and efficacy in a phase 1 trial. Eighteen consecutive patients with RRMM, including 4 with prior murine BCMA CAR exposures, were enrolled. CT103A was administered at 1, 3, and 6 x 10(6) CAR-positive T cells/kg in the dose-escalation phase, and 1 x 10(6) CAR-positive T cells/kg in the expansion cohort. The overall response rate was 100%, with 72.2% of the patients achieving complete response or stringent complete response. For the 4 murine BCMA CAR-exposed patients, 3 achieved stringent complete response, and 1 achieved a very good partial response. At 1 year, the progression-free survival rate was 58.3% for all cohorts and 79.1% for the patients without extramedullary myeloma. Hematologic toxicities were the most common adverse events; 70.6% of the patients experienced grade 1 or 2 cytokine release syndromes. No immune effector cell-associated neurotoxicity syndrome was observed. To the cutoff date, CAR transgenes were detectable in 77.8% of the patients. The median CAR transgene persistence was 307.5 days. Only 1 patient was positive for the anti-drug antibody. Altogether, CT103A is safe and highly active in patients with RRMM and can be developed as a promising therapy for RRMM. Patients who relapsed from prior murine BCMA CAR T-cell therapy may still benefit from CT103A.