INSPIRED Symposium Part 2: Prevention and Management of Relapse Following Chimeric Antigen Receptor T Cell Therapy for B Cell Acute Lymphoblastic Leukemia

Although CD19-directed chimeric antigen receptor (CAR) T cell therapy (CAR-T) for relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) has been transformative in inducing and sustaining remission, relapse rates remain unacceptably high, with approximately 50% of children and young adults experiencing relapse within the first year postinfusion. Emerging strategies to extend the durability of remission involve the use of prognostic biomarkers to identify those at high risk of relapse or incorporate strategies aimed to enhancing functional CAR T cell persistence. Nonetheless, with antigen loss/down-regulation or evolution to lineage switch as major mechanisms of relapse, optimizing single antigen targeting alone is insufficient. Here, with a focus on relapse prevention strategies, including postinfusion surveillance and treatment approaches being explored to optimize post-CAR-T management (eg, combinatorial antigen targeting strategies, preemptive hematopoietic cell transplantation), we review the current state of the art in the prevention and management of post CAR-T relapse. We highlight the advancements in the field and identify gaps in the literature to guide future research in optimizing the prevention and management of post-CAR-T relapse in children and young adults with B-ALL.