COGAAll2131 An International Pilot Study of Chemotherapy and Tyrosine Kinase Inhibitors with Blinatumomab in Patients with Newly-Diagnosed Philadelphia Chromosome-Positive or ABL-class Philadelphia Chromosome-Like B-Cell Acute Lymphoblastic Leukemia

The current 5-year overall survival exceeds 85% for most children diagnosed with acute lymphoblastic leukemia (ALL). However, infants with ALL remain the exception to this success, with 5-year event-free survival (EFS) less than 40% for those with translocations of the KMT2A gene, a genetic driver present in up to 80% of infants with ALL. Clinical trials for infant ALL have increased the dose-intensity of multiagent chemotherapy, however, historically, they have not improved outcomes for KMT2A-rearranged (KMT2A-R) patients due to high relapse rates and dose-limiting toxicities of chemotherapy, highlighting the urgent need to identify innovative therapies. While infants with KMT2A-germline (KMT2A-G) ALL have more favorable outcomes, the high dose intensity of therapy originally developed for KMT2A-R patients leads to an increased risk of short- and long-term toxicity.