Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial

Ming Shi, Jiaojiao Wang, Hongming Huang, Dan Liu, Hai Cheng, Xu Wang, Wei Chen, Zhiling Yan, Wei Sang, Kunming Qi, Depeng Li, Feng Zhu, Zhenyu Li, Jianlin Qiao, Qingyun Wu, Lingyu Zeng, Xiaoming Fei, Weiying Gu, Yuqing Miao, Kailin Xu (), Junnian Zheng () and Jiang Cao ()
Additional contact information
Ming Shi: Xuzhou Medical University
Jiaojiao Wang: The Affiliated Hospital of Xuzhou Medical University
Hongming Huang: The Affiliated Hospital of Nantong University
Dan Liu: Xuzhou Medical University
Hai Cheng: The Affiliated Hospital of Xuzhou Medical University
Xu Wang: Xuzhou Medical University
Wei Chen: The Affiliated Hospital of Xuzhou Medical University
Zhiling Yan: The Affiliated Hospital of Xuzhou Medical University
Wei Sang: The Affiliated Hospital of Xuzhou Medical University
Kunming Qi: The Affiliated Hospital of Xuzhou Medical University
Depeng Li: The Affiliated Hospital of Xuzhou Medical University
Feng Zhu: The Affiliated Hospital of Xuzhou Medical University
Zhenyu Li: The Affiliated Hospital of Xuzhou Medical University
Jianlin Qiao: Jiangsu Bone Marrow Stem Cell Institute
Qingyun Wu: Jiangsu Bone Marrow Stem Cell Institute
Lingyu Zeng: Jiangsu Bone Marrow Stem Cell Institute
Xiaoming Fei: The Affiliated Hospital of Jiangsu University
Weiying Gu: The Third Affiliated Hospital of Soochow University
Yuqing Miao: Yancheng No. People’s Hospital
Kailin Xu: The Affiliated Hospital of Xuzhou Medical University
Junnian Zheng: The Affiliated Hospital of Xuzhou Medical University
Jiang Cao: The Affiliated Hospital of Xuzhou Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells. BC19 CAR T cells also exhibit potent antigen-specific anti-tumor activity in xenograft mouse models. We conduct an open-label, single-arm, phase I/II study of BC19 CAR T cells in 50 patients with R/R MM (ChiCTR2000033567). The primary endpoint was safety. BC19 CAR T cells are well tolerated with grade 3 or higher cytokine release syndrome in 8% of patients and grade 1 neurotoxic events in 4% of patients, which meet the pre-specified primary endpoint. Secondary endpoints include overall response rate (92%), median progression-free survival (19.7 months), median overall survival (19.7 months) and median duration of response (not reached). Our study demonstrates that bispecific BC19 CAR T cells are feasible, safe and effective in treating patients with R/R MM.

Date: 2024
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DOI: 10.1038/s41467-024-47801-8

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