Cancer Gene Therapy

https://doi.org/10.1038/s41417-018-0073-7

Autologous CD19-directed chimeric antigen receptor-T cell is an effective and safe treatment to refractory or relapsed diffuse large B-cell lymphoma

Fang Bao, Wei Wan, Ting He, Feifei Qi, Guanghua Liu, Kai Hu, Xin-an Lu, Ping Yang, Fei Dong, Jing Wang, Hongmei Jing

Received: 11 September 2018 / Revised: 20 November 2018 / Accepted: 1 December 2018

© Springer Nature America, Inc. 2019

Abstract

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Chimeric antigen receptor (CAR) modified T cells targeting CD19 hold great promise to improve the complete response rates of DLBCL patients compared with conventional therapies. Here, we conducted a clinical trial to evaluate the efficacy and safety of CAR-T cells. Five patients with relapsed or refractory DLBCL were treated with autologous T cells expressing the 19-41BBz chimeric antigen receptor (CAR) specifically targeted the CD19 antigen (IM19 CAR-T). The development of cytokine release syndrome (CRS) was observed. And the efficacy of IM19 CAR-T cell treatment was measured with positron emission tomography (PET)–computed tomography (CT). Of the four patients evaluable for response, two obtained complete responses (CRs), one obtained partial response (PR), and one had stable disease (SD). Remarkably, among the five patients, only one developed grade 2 CRS while the others only elicited grade 1 CRS. Additionally, the efficacy and safety of IM19 CAR-T cells were correlated with the peak blood level and persistence of CAR-T cells, as well as the immunophenotype of T-cell subsets. Overall, this study indicates the feasibility and effectiveness of IM19 CAR-T cells in the treatment of refractory or relapsed diffuse large B-cell lymphoma.