A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma

Journal of Hematology & Oncology

Ping Yin¹  Zhihui Wang²  Yimeng Xia³  Dan Jin³  Xinying Zhao⁴  Zhiping Huang⁴  Li Cai⁵  Haiming Kou⁵  Lei Chen⁵  Sha Ke⁵  Chenggong Li⁵  Yu Hu⁵  Lin Liu⁵  Huiwen Jiang⁵  Lisha Ai⁵  Lu Tang⁵  Heng Mei⁵  Chunyan Sun⁵  Jun Deng⁵  Linghui Xia⁵  Tao Guo⁵  Gaoquan Hua⁶ 

[1] Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology;Drug Clinical Trial Institution, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology;Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease;Institute of Hematology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University;Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology;Zhejiang Cellyan Biotechnology Co. Ltd;

关键词: Chimeric antigen receptor-T cells;    Multiple myeloma;    BCMA;    CD38;    Bispecific CAR;   

DOI  :  10.1186/s13045-021-01170-7

来源: DOAJ

【 摘 要 】

Abstract Background BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations. Methods We constructed a humanized bispecific BM38 CAR targeting BCMA and CD38 and tested the antimyeloma activity of BM38 CAR-Ts in vitro and in vivo. Twenty-three patients with RRMM received infusions of BM38 CAR-Ts in a phase I trial. Results BM38 CAR-Ts showed stronger in vitro cytotoxicity to heterogeneous MM cells than did T cells expressing an individual BCMA or CD38 CAR. BM38 CAR-Ts also exhibited potent antimyeloma activity in xenograft mouse models. In the phase I trial, cytokine release syndrome occurred in 20 patients (87%) and was mostly grade 1–2 (65%). Neurotoxicity was not observed. Hematologic toxicities were common, including neutropenia in 96% of the patients, leukopenia in 87%, anemia in 43% and thrombocytopenia in 61%. At a median follow-up of 9.0 months (range 0.5 to 18.5), 20 patients (87%) attained a clinical response and minimal residual disease-negativity (≤ 10–4 nucleated cells), with 12 (52%) achieving a stringent complete response. Extramedullary plasmacytoma was eliminated completely in 56% and partially in 33% and of 9 patients. The median progression-free survival was 17.2 months. Two relapsed patients maintained BCMA and CD38 expression on MM cells. Notably, BM38 CAR-Ts cells were detectable in 77.8% of evaluable patients at 9 months and 62.2% at 12 months. Conclusion Bispecific BM38 CAR-Ts were feasible, safe and significantly effective in patient with RRMM. Trial registration: Chictr.org.cn ChiCTR1800018143.

【 授权许可】

Unknown