Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma

作者：Xiaoyan Qu, Gang An, Weiwei Sui, Tingyu Wang, Xian Zhang, Junfang Yang, Yan Zhang, Lu Zhang, Dan Zhu, Jiaqi Huang, Shigui Zhu, Xin Yao, Jing Li, Jing Li, Chengxiao Zheng, Kevin Zhu, Yutian Wei, Xiaoteng Lv, Liping Lan, Yihong Yao, Daobin Zhou, Peihua Lu, Lugui Qiu, Jianyong Li, Jianyong Li · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2022 · 被引用次数：32 · 研究领域：CAR-T cell therapy research、Multiple Myeloma Research and Treatments、Viral Infectious Diseases and Gene Expression in Insects

Background Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy showed remarkable efficacy in patients with relapsed or refractory multiple myeloma (RRMM). This phase 1 dose-escalation and expansion study developed C-CAR088, a novel second-generation humanized anti-BCMA CAR T-cell therapy, and assessed the safety and efficacy of three dosages of C-CAR088 in patients with RRMM. Methods Patients received lymphodepletion with three doses of cyclophosphamide (300 mg/m2) and three doses of fludarabine (30 mg/m2) on days –5, –4, and –3, followed by an infusion of C-CAR088 on day 0. Doses of 1.0×106, 3.0×106, and 6.0×106 CAR T cells/kg (±20%) were tested in the dose-escalation cohorts and expansion cohorts. The primary endpoint was treatment safety, including the rate of treatment-emergent adverse events after cell infusion. Secondary endpoints were the overall response rate and progression-free survival. The exploratory endpoints were the quantification of C-CAR088 CAR T cells, selection of cytokines and chemokines in blood, and measurement of tumor BCMA expression. Results As of July 2, 2021, 31 patients had been infused with C-CAR088. Any grade cytokine release syndrome (CRS) occurred in 29 patients (93.5%), and grade 3 CRS occurred in 3 patients (9.7%). One patient from the high-dose group (4.5–6.0×106 CAR T cells/kg) developed grade 1 neurotoxicity. No dose-limiting toxicities were observed in any dose group, and all adverse events were reversi...