Optimizing CAR-T cell therapy in adults with B-cell acute lymphoblastic leukemia

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated unprecedented success in the treatment of various hematologic malignancies including relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Currently, there are two FDA-approved CD19-directed CAR-T cell products for the treatment of adults with R/R B-ALL. Despite high remission rates following CD19 CAR-T cell therapy in R/R B-ALL, remission durability remains limited in most adult patients, with relapse observed frequently in the absence of additional consolidation therapy. Furthermore, the burden of CAR-T cell toxicity remains significant in adults with R/R B-ALL and further limits the wide utilization of this effective therapy. In this review, we discuss patient and disease factors that are linked to CAR-T cell therapy outcomes in R/R B-ALL and strategies to optimize durability of response to reduce relapse and mitigate toxicity in the adult population. We additionally discuss future approaches being explored to maximize the benefit of CAR-T in adults with B-ALL.