With BiTEs at the kiddie table, where do CARs come in for pediatric B-ALL?

T-cell engaging immunotherapies have transformed the treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL). First revolutionizing outcomes for relapsed and refractory disease, these therapies are now being incorporated and studied in the frontline setting. With the US Food and Drug Administration (FDA) approval of the CD19-directed bispecific T-cell engager (BiTE) blinatumomab for remission consolidation, the majority of patients with B-ALL receive blinatumomab in frontline therapy. Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 is FDA approved for pediatric patients with B-ALL that is refractory or in second or greater relapse. With the same target, similar mechanisms of action, and some overlap in indications, the optimal placement and sequence of these immunotherapies remain unclear. Here we review the recent data and expanded use of blinatumomab and CAR T-cell therapy and discuss the role of CAR T-cell therapy in the current pediatric B-ALL treatment landscape, including in populations with relapsed/refractory disease and at very high risk of relapse.