CD19 CAR-T expressing PD-1/CD28 chimeric switch receptor as a salvage therapy for DLBCL patients treated with different CD19-directed CAR T-cell therapies

Aibin Liang,Wen Lei,Ping Li,Zheming Lu,Ken H. Young,Wenbin Qian,Chaoting Zhang,Yun Liang,Hui Liu

doi:10.1186/s13045-021-01044-y

Abstract

CD19-targeted chimeric antigen receptor T (CAR T) cell therapy is a promising option to treat relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). However, the majority of CAR T-treated patients will eventually progress and require salvage treatment, for which there is no current standard. In this study, we analyzed data from 6 patients with R/R DLBCL who experienced progression following CD19-CAR T therapy, and then received CD19-specific CAR T cells that express a PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR T) as salvage therapy at our institution. After the second infusion of CAR T cells, 3 of 6 patients achieved complete remissions and the duration of the response of responsive patients ranged from 8 to 25 months. One patient showed a stable disease. In contrast, 2/6 patients died on 60 days because of progression disease. Importantly, no severe neurologic toxicity or cytokine release syndrome was observed. These data suggest that CD19-PD-1/CD28-CAR-T cells, a novel anti-CD19 CAR-T cell therapy, elicit a potent and durable anticancer response, and can be used in the post-CD19-CAR T failure setting.

Highlights

CD19-targeted chimeric antigen receptor T (CAR T) cell therapy is a promising option to treat relapsed/refractory diffuse large B-cell lymphoma (R/R Relapsed/refractory diffuse large B-cell lymphoma (DLBCL))
To the Editor: CD19-specific CAR T cell therapy has significantly improved the outcome of patients with R/R DLBCL, resulting in durable remissions in approximately 40% of heavily pretreated patients
*Correspondence: lab7182@tongji.edu.cn; ken.young@duke.edu; qianwb@zju.edu.cn †Yun Liang, Hui Liu and Zheming Lu are co-first author 1 Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China 3 Department of Hematology, Tongji Hospital of Tongji University, Shanghai, People’s Republic of China 4 Hematopathology Division and Department of Pathology, Duke University Medical Center and Cancer Institute, Durham, NC, USA Full list of author information is available at the end of the article durable response after CD19-CAR T therapy and a significant proportion of patients will eventually relapse and develop treatment-refractory, fatal disease [1–4]

Summary

Introduction

CD19-targeted chimeric antigen receptor T (CAR T) cell therapy is a promising option to treat relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). *Correspondence: lab7182@tongji.edu.cn; ken.young@duke.edu; qianwb@zju.edu.cn †Yun Liang, Hui Liu and Zheming Lu are co-first author 1 Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China 3 Department of Hematology, Tongji Hospital of Tongji University, Shanghai, People’s Republic of China 4 Hematopathology Division and Department of Pathology, Duke University Medical Center and Cancer Institute, Durham, NC, USA Full list of author information is available at the end of the article durable response after CD19-CAR T therapy and a significant proportion of patients will eventually relapse and develop treatment-refractory, fatal disease [1–4].

Results

Conclusion