Azacitidine–Venetoclax or Induction Chemotherapy for Acute Myeloid Leukemia

Azacitidine–Venetoclax or Induction Chemotherapy for Acute Myeloid Leukemia Published September 2, 2026 N Engl J Med 2026;395:845-858 DOI: 10.1056/NEJMoa2602804 Abstract Background 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. For patients who are ineligible for induction chemotherapy, hypomethylating therapy plus venetoclax is the standard treatment owing to its efficacy and side-effect profile. Methods In this multicenter, phase 2 trial, we randomly assigned, in a 1:1 ratio, previously untreated adults with AML who were eligible for induction chemotherapy to receive either azacitidine plus venetoclax or induction chemotherapy. Patients with core binding factor fusions, mutations in the gene encoding FMS-like tyrosine kinase 3 (FLT3), or mutations in the gene encoding nucleophosmin-1 (NPM1; unless the patient was ≥60 years of age) were excluded. The primary end point was event-free survival. Results A total of 172 patients underwent randomization, with 86 patients assigned to each group. The median age of the patients was 64 years. A total of 72% of the patients had adverse-risk disease according to the European LeukemiaNet 2022 classification. At a median follow-up of 21.9 months, the median event-free survival was 14.5 months (95% confidence interval [CI], 10.4 to 24.4) in the azacitidine–venetoclax group, as compared with 6.2 months (95% CI, 4.1 to 10.1) in the induction chemotherapy group, corresponding to a hazard ratio for event or death of 0.57 (95% CI, 0.39 to 0.84; P=0.002 by the stratified log-rank test). Infection of grade 3 or higher occurred in 28% of the patients (95% CI, 19 to 39) receiving azacitidine–venetoclax and in 41% of those (95% CI, 30 to 52) receiving induction chemotherapy; hemorrhage of grade 3 or higher occurred in 2% (95% CI, 0.3 to 8) and 12% (95% CI, 6 to 20), respectively. Conclusions In this phase 2, randomized trial, azacitidine–venetoclax therapy led to significantly longer event-free survival than induction chemotherapy among induction-eligible patients with AML. (Funded by AbbVie and others; PARADIGM ClinicalTrials.gov number, NCT04801797.) Are you a member of an institution such as a university or hospital?Learn more about Institutional Access Notes A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Supported by AbbVie and Genentech and by a Harvard Cancer Center Support Grant (5P30 CA006516). Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the patients and their families for their participation in this trial; the staff of the Program for Coordination of Research Protocols in the Massachusetts General Hospital (MGH) Cancer Center Protocol Office for the multicenter coordination and monitoring of the trial; and Aura Ramos, Tina Som, Megan Vartanian, Sara Ruiz, Laura White, Christine Connolly, and Shannon Himber, of the MGH clinical trial research team, for their efforts during the conception and conduct of this trial. Supplementary Material Information & Authors Information Published In Copyright Copyright © 2026 Massachusetts Medical Society. All rights reserved. For personal use only. Any commercial reuse of NEJM Group content requires permission. History Published online: September 2, 2026 Published in issue: September 3, 2026 Topics Authors Metrics & Citations Metrics Altmetrics Citations Export citation Select the format you want to export the citation of this publication. Cited by - Hypomethylating Agents plus Venetoclax as Compared with Intensive Chemotherapy in Patients with AML, New England Journal of Medicine, 395, 9, (917-919), (2026)./doi/full/10.1056/NEJMe2607967 Loading...