The future of cellular immunotherapy for childhood leukemia.

PURPOSE OF REVIEW: Exciting translational discoveries in recent years have brought realized promise of immunotherapy for children with high-risk leukemias. This review summarizes the current immunotherapeutic landscape with a focus on key clinical trials for patients with acute lymphoblastic leukemia or acute myeloid leukemia.

RECENT FINDINGS: Chemotherapy resistance remains a major barrier to cure in children with high-risk leukemias. Immunotherapy approaches have potential to overcome this resistance given alternative mechanisms of action. Based upon preclinical activity and/or success in adult patients, recent clinical trials have demonstrated safety and efficacy of various mAb, antibody-drug conjugate, bispecific T-cell-engaging antibody, natural killer cell, and chimeric antigen receptor-redirected T-cell immunotherapies for children with acute lymphoblastic leukemia or acute myeloid leukemia. Food and Drug Administration approval of several of these immunotherapies has increased the pediatric leukemia therapeutic portfolio and improved clinical outcomes for previously incurable patients.

SUMMARY: Several antibody-based or cellular immunotherapy modalities have demonstrated appreciable efficacy in children with relapsed or chemotherapy-refractory leukemia via early-phase clinical trials. Some studies have also identified critical biomarkers of treatment response and resistance that merit further investigation. Continued preclinical and clinical evaluation of novel immunotherapies is imperative to improve cure rates for children with high-risk leukemias.