AML-063: A Randomized, Double-Blind, Placebo-Controlled Study of Venetoclax with Azacitidine Versus Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia Ineligible for Intensive Therapy-Viale-A

Aims We evaluated efficacy of Azacitidine (AZA)+Venetoclax (VEN) combination vs. AZA+Placebo (PBO) in treatment-naive patients with acute myeloid leukemia (AML) ineligible for intensive therapy. Methods This phase 3, randomized, double-blinded, multicenter, placebo-controlled study included AML patients ineligible for intensive induction therapy due to medical comorbidities and/or age > 75 years. Patients were randomized 2:1 to either AZA+VEN(AZA: 75 mg/m2 subcutaneous or intravenous, days [d] 1-7 per 28-day cycle; VEN: 400 mg orally QD, d1-28 with 3-day ramp up in cycle 1) or AZA+PBO (PBO: orally QD, d1–28). Primary endpoint was overall survival (OS). Secondary endpoints were rates of: composite complete remission [complete remission (CR) + CR with incomplete count recovery (CRi)], CR+CRi by initiation of cycle 2, CR, transfusion independence, CR+CRi and OS by molecular subgroups, and event-free survival (EFS). A sample size of 400 was estimated to detect a hazard ratio (HR) of 0.7 in OS with 2-sided alpha of 4% and power of 87%. OS and EFS were analyzed by the Kaplan-Meier method and compared between arms using the log-rank test stratified by age (18 to Results As of 01/04/2020, 431 patients (median age 76 years, range 49-91) were randomized to AZA+VEN (n=286) or AZA+PBO (n=145). With median follow-up of 20.5 months (mos), median OS was 14.7 mos in AZA+VEN and 9.6 in AZA+PBO (HR: 0.66, 95% CI: 0.52–0.85, p Conclusions Among treatment-naive predominantly elderly patients with AML ineligible for intensive therapy, combination AZA+VEN showed statistically significant and clinically meaningful improvement in response rates and OS vs AZA, with a manageable safety profile. Abstract was previously published at EHA25.