Maintenance after CAR T? Are we there yet? Reducing the risk of relapse after loss of anti-CD19 CAR T - cell persistence in ALL

Abstract Anti-CD19 chimeric antigen receptor (CAR) T cells can induce complete remission in the majority of children and young adults affected by multiple relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL) and provide potential long-term cure through continuous surveillance against leukemic recurrence. The presence of B-cell aplasia represents an indirect marker of CAR T functional persistence. Patients treated with tisagenlecleucel who present with early (within 6 months from infusion) B-cell recovery (BCR) have an increased risk of relapse and merit further treatment. In this work, we describe a pediatric clinical scenario and discuss the possible interventions—that is, hematopoietic stem cell transplantation (HSCT), second CAR T infusion, and maintenance chemotherapy—for similar patients with early BCR after CAR T, based on the available literature. We advocate for HSCT with total body irradiation (TBI) in children who had never received transplantation and can safely undergo TBI, while those who already had a first HSCT with TBI or present with a contraindication to TBI, in the absence of available clinical trials, can be considered for maintenance chemotherapy, given early indications of good tolerability and promising noninferior outcomes. Patients with Philadelphia-positive ALL should receive tyrosine kinase inhibitors in the context of either HSCT or maintenance chemotherapy. For young adults, 3 different commercial CAR T are available, but so far, clinical data are insufficient to support any specific consolidation strategy.