The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia

Chimeric antigen receptor (CAR) T cells have demonstrated remarkable ability to render multiple relapsed and refractory patients into a deep and often durable remission. Since initial FDA approval of tisagenlecleucel in 2017, real-world data have shown the benefit of this therapy, even among historically complex populations, such as infants, children with Down syndrome, and those with extramedullary leukemia. Despite the success of CAR T cell therapy, nearly half of patients tend to show relapsed disease, demanding ongoing advancements. Furthermore, the incorporation of the bispecific T cell engager, blinatumomab, into B cell acute lymphoblastic leukemia (B-ALL) therapy has fundamentally shifted the treatment paradigm, calling for a reevaluation of the optimal application of CAR T cells. In this review, we describe the current usage of CAR T cells in children, adolescents, and young adults (CAYAs) with B-ALL and discuss anticipated changes to CAR T cell therapy and post-infusion management. Upfront use of blinatumomab will require novel approaches to relapsed disease, including the use of CAR T cells earlier in therapy. Limited durability of the currently approved CAR T cells will require novel constructs along with improved toxicity mitigation and refinements in post-CAR disease surveillance and therapy. While CAR T cells have made an incredible impact on the field, there is much work due to improve outcomes for CAYAs with B-ALL.