Determinants of outcomes and advances in CD19‐directed chimeric antigen receptor therapy for B‐cell acute lymphoblastic leukemia

Abstract

Relapsed and refractory B‐cell acute lymphoblastic leukemia (B‐ALL) is an aggressive B‐cell neoplasm associated with poor outcomes. Conventional multiagent chemotherapy and bispecific antibody therapy may induce remission; however, relapse rates remain high and overall survival is poor. Chimeric antigen receptor T‐cell (CAR‐T) therapy provides durable, deep complete remission, and long‐term cures in relapsed and refractory B‐ALL. However, with this new treatment modality, 10%–30% of patients do not achieve remission, and over 50% experience relapse after therapy. Currently, there are two approved CD19‐specific CAR‐T cell constructs in B‐ALL, Tisagenlecleucel and Brexucabtagene Autoleucel by the United States Food and Drug Administration, and the European Medicines Agency (EMA). In this review, we discuss patients, disease, and CAR‐T predictors of outcomes in B‐ALL. We describe the two approved CD19‐directed CAR‐T cell products, review the current literature, and discuss factors associated with high risks of therapy failure and future direction in CAR‐T cell therapy for B‐ALL.