Beyond Cellular Therapies: The Expanding Role of Antibody-Driven Immunotherapy in Pediatric Acute Lymphoblastic Leukemia.

Abstract

Background: The integration of novel antibody-mediated targeted therapies into both relapsed/refractory (R/R) and frontline pediatric acute lymphoblastic leukemia (ALL) treatment protocols has led to critical advancements in the field. Current research efforts focus on optimizing targeted therapies to enhance precision and efficacy while minimizing toxicity by reducing chemotherapy. A notable example is the addition of blinatumomab demonstrating superiority of over conventional chemotherapy, with an 8% increase in disease-free survival (DFS) at an interim analysis, reaching 96%. Inotuzumab ozogamicin (InO) has also shown promise, achieving nearly a 70% complete response (CR) rate in pediatric R/R B-cell ALL (B-ALL) trials. Additionally, daratumumab in T-cell ALL (T-ALL) and chimeric antigen receptor (CAR) T-cell therapies, particularly CD19-directed (B-ALL) and CD7-directed (T-ALL) strategies are under active investigation.

Summary: This review will provide an overview of targeted antibody-mediated immunotherapies in both B-ALL and T-ALL, with a focus on their pediatric applications, supporting data, and future prospects.

Key messages: The next cycle of front-line trials in pediatric ALL will incorporate more immunotherapy with reduction of chemotherapy. Subsequent trials will utilize more concurrent chemoimmunotherapy blocks as precision testing and risk-adapted therapy will continue to develop. These advancements reflect a paradigm shift toward more precise, less toxic treatment strategies in pediatric ALL.