Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients

Abstract

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade≥3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.

Keywords

CAR-T cell therapy / refractory diffuse large B-cell lymphoma / cytokine release syndrome / dose-limiting toxicity

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Acknowledgements

This study was sponsored by Cellular Biomedicine Group Inc. and partly by National Natural Science Foundation of China (No. 81720108002), Major Program of National Natural Science Foundation of China (No. 2018ZX09734-007), and Jiangsu Provincial Special Program of Medical Science (No. BE2017751).

Compliance with ethics guidelines

Lei Fan, Li Wang, Lei Cao, Huayuan Zhu, Wei Xu, and Jianyong Li declare no conflict of interests. All procedures were performed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and the Helsinki Declaration of 1975 as revised in 2000 (5). Informed consent was obtained from all patients.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-021-0843-8 and is accessible for authorized users.

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