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How We Use Risk Factors for Success or Failure of CD19 CAR T-cells to Guide Management of Children/AYA with B-cell ALL.

By overcoming chemotherapeutic resistance, chimeric antigen receptor (CAR) T-cells facilitate deep complete remissions and offer the potential for long-term cure in a substantial fraction of patients with chemotherapy refractory disease. However, that success is tempered with 10-30% of patients not achieving remission and over half of patients treated eventually experiencing relapse. With over a decade of experience using CAR T-cells in children, adolescents, and young adults (AYA) to treat relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and 5 years since the first FDA approval, data defining nuances of patient-specific risk factors are emerging. With the commercial availability of 2 unique CD19 CAR T-cell constructs for B-ALL, in this article we review the current literature, outline our approach to patients and discuss how individual factors inform strategies to optimize outcomes in children and AYA receiving CD19 CAR T-cells. We include data from both prospective and recent large retrospective studies that offer insight into understanding when risks of CAR T-cell therapy failure are high and offer perspectives suggesting when consolidative hematopoietic cell transplantation (HCT) or experimental CAR T-cell and/or alternative immunotherapy should be considered. We also propose areas where prospective trials addressing optimal use of CAR T-cell therapy are needed.