医学
多发性骨髓瘤
嵌合抗原受体
不利影响
内科学
肿瘤科
免疫学
来那度胺
细胞因子释放综合征
胃肠病学
免疫疗法
癌症
作者
Di Wang,Jue Wang,Gang Hu,Wen Wang,Yi Xiao,Haodong Cai,Lijun Jiang,Meng Li,Yongkun Yang,Xiaoxi Zhou,Zhenya Hong,Zheng Yao,Min Xiao,Liting Chen,Xia Mao,Li Zhu,Jin Wang,Lugui Qiu,Chunrui Li,Jianfeng Zhou
出处
期刊:Blood
[American Society of Hematology]
日期:2021-01-21
被引量:123
标识
DOI:10.1182/blood.2020008936
摘要
B cell maturation antigen- (BCMA) specific chimeric antigen receptor (CAR) T-cell therapies have shown efficacy in relapsed, refractory multiple myeloma (RRMM). Since the non-human originated antigen-targeting domain may limit clinical efficacy, we developed a fully human BCMA-specific CAR, CT103A, and report its safety and efficacy in a phase I trial. Eighteen consecutive RRMM patients, including four patients with prior murine BCMA CAR exposures, were enrolled. CT103A was administered at 1, 3, and 6 × 106 CAR-positive T cells/kg in the dose-escalation phase, and 1 × 106 CAR-positive T cells/kg in the expansion cohort. The overall response rate (ORR) was 100%, with 72.2% of the patients achieving complete response or stringent complete response (sCR). For the four murine BCMA CAR-exposed patients, three achieved sCR, and one achieved a very good partial response. At one 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 one patient was positive for the anti-drug antibody. Altogether, CT103A is safe and highly active in RRMM patients 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. (Chinese Clinical Trial Registry ChiCTR1800018137)
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