Multicenter randomized phase 2 trial of azacitidine-venetoclax or induction chemotherapy for acute myeloid leukemia

Induction chemotherapy has long been a key component of curative therapy for fit patients with acute myeloid leukemia (AML), despite its frequently severe side effects and substantial health care utilization. In the multicenter phase 2 PARADIGM trial, previously untreated AML who were eligible for induction chemotherapy were randomized (1:1) to receive either azacitidine plus venetoclax (n=86) or induction chemotherapy (n=86); patients with core binding factor fusions, FLT3 mutations, or NPM1 mutations (unless the patient was ≥ 60 years of age) were excluded. The primary endpoint was event-free survival (EFS). At a median follow-up of 21.9 months, the median EFS was 14.5 months in the azacitidine-venetoclax group and 6.2 months in the induction chemotherapy group (HR 0.57; 95% CI 0.39-0.84). Infection of grade 3 or higher occurred in 28% versus 41%, and hemorrhage of grade 3 or higher in 2% versus 12%, respectively. The authors conclude that in this study , first-line azacitidine-venetoclax therapy led to significantly longer EFS than induction chemotherapy among induction-eligible patients with AML (quick take video summary).