Challenges and advances in CAR-T cell therapy for B-ALL

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment landscape for hematological malignancies such as relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), with several CAR-T products now approved globally for R/R B-ALL. Despite high initial response rates, major challenges remain, including disease relapse due to antigen escape and the limited persistence of CAR-T cells; treatment-related adverse events such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, hematologic toxicity, and infections; and limited access to CAR-T therapy. In this review, we discuss the limitations of CAR-T and strategies to overcome them, specifically in the context of B-ALL, including the use of allogeneic CAR-T, dual-targeted CAR-T, and combination strategies with novel technologies and agents. Furthermore, we explored the role of consolidative allogeneic hematopoietic stem cell transplantation after CAR-T therapy and the potential of integrating CAR-T into the first-line treatment for B-ALL. Future research should aim to increase the efficacy of CAR-T, reduce their toxicity, improve their accessibility, and expand their use to earlier lines of therapy for B-ALL.