A Phase I Clinical Trial of Chimeric Antigen Receptor-Modified T Cells in Patients with Relapsed and Refractory Lymphoma
Xinfeng Chen, Xin Li, Yanfen Liu, Zhen Zhang, Xudong Zhang, Jianmin Huang, Hong Li, Feng Li, Lei Zhang, Ling Li, Xiaolong Wu, Wang Ma, Zhenchang Sun, Hui Yu, Zhi‐Yuan Zhou, Xiaoyan Feng, Kang Cui, Zhaoming Li, Hongling Zhang, Ying Zeng, Xiaochun Wan, Youhai H. Chen, Mingzhi Zhang, Yi Zhang
Abstract
Aim: CD19 chimeric antigen receptor (CAR) T cells have been approved by the US FDA for treatment of relapsed and refractory (R/R) B-cell malignancies. Patients & methods: This study investigated the safety and efficacy of autologous 4-1BB costimulatory domain-engineered CD19 CAR-T cells in R/R B-cell lymphoma. Results: After CD19 CAR-T-cell infusion, severe cytokine release syndrome occurred in 28.6% (4/14) of the patients. The overall response rate was 77% with complete remission observed in 6/14 patients at 3 months. A higher tumor burden and grade 3–4 of myelosuppression after chemotherapy were associated with severe cytokine-release syndrome. Notably, combining CD19 CAR-T cells and PD-1 blockade, but not CD19 CAR-T cells alone, reduced intracranial tumor burden in a patient with central invasion of lymphoma. Conclusion: CD19 CAR-T cells could effectively induce tumor remission and PD-1 blockade might improve the efficacy in Chinese patients with R/R B-cell lymphoma.