The mechanisms and salvage treatment strategies underlying positive relapse following CD19 CAR-T cell therapy in B-acute lymphoblastic leukemia
10.3760/cma.j.cn121090-20240701-00242
- VernacularTitle:急性B淋巴细胞白血病CD19 CAR-T细胞治疗后阳性复发的机制和挽救性治疗策略
- Author:
Cong LU
1
;
Jia XU
;
Heng MEI
Author Information
1. 华中科技大学同济医学院附属协和医院血液科，湖北省肿瘤疾病细胞治疗临床医学研究中心，武汉 430022
- From:
Chinese Journal of Hematology
2024;45(10):970-976
- CountryChina
- Language:Chinese
-
Abstract:
Approximately 50% of patients suffering from relapsed/refractory B-acute lymphoblastic leukemia (R/R B-ALL), experience relapse within one year, with around 60% of these relapses being antigen-positive, despite the transformative impact of chimeric antigen receptor (CAR) T cell therapy. The mechanisms underlying relapse are primarily associated with tumor heterogeneity, CAR-T cell dysfunction, subopimal in vivo expansion and persistence, and an inhibitory immune microenvironment. This review aims to investigate salvage strategies designed to enhance outcomes for patients undergoing relapse or disease progression following the CAR-T cell therapy. These strategies include a second CAR-T cell infusion that targets either the same antigen or an alternative target, the administration of immune checkpoint inhibitors, and the utilization of novel targeted therapies including monoclonal antibodies, antibody-conjugated drugs and small molecule compounds aimed at mitigating CD19-positive relapse or overcoming CAR-T cell resistance. Nevertheless, achieving improved long-term survival for these patients continues be challenging.
