Despite recent therapeutic advances, outcomes remain poor for older patients with acute myeloid leukemia (AML).For patients in the USA diagnosed with AML between 2010 - 2017, the 5-yr overall survival (OS) rate was 22% for patients aged 60 - 69 years, and only 5% for those aged ≥ 70 years.Survival outcomes are influenced by patient- and disease-related factors, including age, comorbidities, cytogenetic abnormalities, gene mutations, and persistence of leukemic cells after intensive chemotherapy (IC) (i.e., measurable residual disease [MRD]).There is a need for effective maintenance therapies to prolong survival among HSCT-ineligible patients in complete remission.In the randomized, double-blind, phase 3 QUAZAR AML-001 trial, oral azacitidine (Oral-AZA) significantly prolonged OS and relapse-free survival (RFS) vs. placebo in patients ≥ 55 years with AML in first remission after IC who were not HSCT candidates.Here, we present updated OS outcomes (data cutoff March 2022) with the median follow-up time now 55.5 mo and investigate clin. and biol. variables predictive of long-term survival, defined here as survival ≥ 3 years from randomization, in patients treated with Oral-AZA or placebo.Briefly, patients aged ≥ 55 years with intermediate-or poor-risk cytogenetics at diagnosis who achieved first complete remission (CR) or CR with incomplete blood count recovery (CRi) with IC, were randomized 1:1 to receive Oral-AZA 300-mg or placebo once-daily for 14 days in repeated 28-day cycles.OS was estimated by Kaplan-Meier methods and compared between treatment groups by stratified log-rank test. NPM1 and FLT3 gene mutations (mut) were assessed locally at diagnosis for most patients; post-IC MRD status was assessed centrally at study screening by multiparameter flow cytometry.Estimated 3-yr survival rates in the Oral-AZA and placebo arms were 37.4% and 27.9%, resp. ( Δ + 9.5% with Oral-AZA [95%CI + 0.9% to + 18.1%]); 5-yr survival rates were 26.5% vs. 20.1% ( Δ + 6.3% [95%CI 2.1% to + 14.7%]).The model included randomized treatment arm (Oral-AZA vs. placebo), NPM1 status ( NPM1 mut vs. NPM1 wt ) at diagnosis, cytogenetic risk (poor vs. intermediate) at diagnosis, MRD status (MRD + vs. MRD - )at screening, and absolute neutrophil count (continuous variable) at screening.In conclusion, these updated findings demonstrate the feasibility and sustained long-term clin. benefit of Oral-AZA maintenance, now with over 4 years of median follow-up time for patients in remission after chemotherapy.Patients with AML completing intensive induction and consolidation therapy should therefore be strongly considered for Oral-AZA maintenance, particularly those for whom HSCT may not be feasible or initially indicated, including patients with favorable risk NPM1 mutated disease.