A New Combination Approach to KMT2A-Rearranged Infant Leukemia | Dr. Lisa Niswander

How can pairing living CAR T-cell immunotherapy with targeted menin inhibitors overcome rapid relapse and chemotherapy toxicity in KMT2A-rearranged infant leukemia? Infant acute lymphoblastic leukemia (ALL) represents one of the most challenging hematologic malignancies in pediatric oncology, characterized by aggressive biology, rapid treatment resistance, and severe vulnerability to high-dose cytotoxic regimens. In this 12-minute interview with Oncology Data Advisor, Lisa Niswander, MD, PhD, Physician-Scientist at Roswell Park Comprehensive Cancer Center and the Roswell Park Golisano Children’s Buffalo Cancer and Blood Disorders Program, outlines an innovative combination approach pairing CD19-directed CAR T-cell therapy with targeted menin inhibitors for infants harboring KMT2A gene rearrangements. Read the full accompanying article on Oncology Data Advisor: https://bit.ly/48ep27g What You Will Learn in This Episode 🔹 Distinct Biology of KMT2A-Rearranged Infant ALL: Why leukemia diagnosed under 12 months of age is biologically distinct from older pediatric and adult disease, driven in approximately 80% of cases by a single oncogenic KMT2A gene rearrangement. 🔹 Overcoming Chemoresistance and Developmental Toxicities: How KMT2A fusion proteins drive rapid resistance to conventional chemotherapy and why reducing reliance on high-dose cytotoxic regimens is critical for infants undergoing key developmental milestones. 🔹 Synergizing CAR T-Cell Therapy With Menin Inhibition: Exploring preclinical data showing that combining CD19-directed CAR T cells with orally bioavailable menin inhibitors outperforms either modality alone in infant ALL models. 🔹 Mechanistic Considerations for Living Therapies: Understanding how small-molecule targeted inhibitors interact with living cellular immunotherapies and investigating whether menin inhibition enhances CAR T-cell persistence, metabolic fitness, and cytotoxicity.