Harnessing the Immune System: Current and Emerging Immunotherapy Strategies for Pediatric Acute Lymphoblastic...

Treatment for relapsed acute lymphoblastic leukemia (ALL) in children and young adults continues to evolve. Despite optimization of cytotoxic chemotherapeutic approaches and risk-adapted therapy, about 12% of pediatric patients still relapse, and survival rates in this population remain poor. Salvage therapy for relapsed patients continues to be challenging as attempts to further intensify chemotherapy have resulted in excessive toxicity without improving outcomes. Immunotherapy has profoundly impacted the landscape of relapsed ALL by harnessing the patient's immune system to target and eliminate leukemia cells. In this review, we provide an overview and summary of immunotherapy agents that have been approved and remain under investigation for children, including blinatumomab, inotuzumab, daratumomab, and chimeric antigen receptor T-cell therapy. We discuss the landmark clinical trials that have revolutionized the field and provide an update on ongoing clinical trials involving these agents for children in the relapsed and upfront setting. The incorporation of these novel immunotherapies into ALL treatment, either as monotherapy or in combination with cytotoxic chemotherapy, has demonstrated promising potential to augment outcomes while decreasing toxicity. However, we also highlight the many challenges we still face and the research critically needed to achieve our goals for cure in children.