The present and future of CAR T-cell therapy for adult B-cell ALL

Abstract

Chimeric antigen receptor T-cell therapy (CAR-T) targeting CD19 has transformed the management of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), with the US Food and Drug Administration approval of tisagenlecleucel for pediatric/young adult patients and brexucabtagene autoleucel for adults. Efficacy is contingent upon several factors including disease burden. Emerging data suggest that bridging therapy, lymphodepletion, and, for some patients, consolidation therapy have an important role in the success of treatment. Furthermore, strategies to define and manage immunotoxic side effects including hematotoxicity is critical to safe delivery. Advancements in CAR-T design beyond CD19 represent an ongoing therapeutic evolution. Overall, CAR-T signifies a paradigm shift in B-ALL management, with the potential for improved remission and survival in a historically challenging patient population.