RT Journal Article
SR Electronic
T1 Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e005145
DO 10.1136/jitc-2022-005145
VO 10
IS 9
A1 Qu, Xiaoyan
A1 An, Gang
A1 Sui, Weiwei
A1 Wang, Tingyu
A1 Zhang, Xian
A1 Yang, Junfang
A1 Zhang, Yan
A1 Zhang, Lu
A1 Zhu, Dan
A1 Huang, Jiaqi
A1 Zhu, Shigui
A1 Yao, Xin
A1 Li, Jing
A1 Zheng, Chengxiao
A1 Zhu, Kevin
A1 Wei, Yutian
A1 Lv, Xiaoteng
A1 Lan, Liping
A1 Yao, Yihong
A1 Zhou, Daobin
A1 Lu, Peihua
A1 Qiu, Lugui
A1 Li, Jianyong
YR 2022
UL http://jitc.bmj.com/content/10/9/e005145.abstract
AB 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 reversible after proper management. The overall response, stringent complete response, complete response (CR), and very good partial response rates were 96.4%, 46.4%, 10.7%, and 32.1%, respectively. The CR rate in the medium-dose (3.0×106 CAR T cells/kg) and high-dose (4.5–6.0×106 CAR T cells/kg) groups was 54.5% and 71.4%, respectively. In the CR group, 15 (93.7%) patients achieved minimal residual disease (MRD) negativity (test sensitivity >1/10−5). All seven patients with double-hit or triple-hit multiple myeloma achieved MRD-negative CR.Conclusions The present study demonstrated that C-CAR088 had a good safety profile and high antitumor activity in patients with RRMM, constituting a promising treatment option for RRMM.Trial registration number NCT03815383, NCT03751293, NCT04295018, and NCT04322292.Data are available upon reasonable request. Data are available upon reasonable request. Following publication de-identified individual patient data may be shared with qualifying researchers by request with a research proposal. Requests should be directed to the corresponding author. The corresponding author had full access to all data and had final responsibility for the decision to submit the results for publication.