AML-457 Oral Azacitidine (Oral-AZA) in Patients With Acute Myeloid Leukemia (AML) in First Remission after Intensive Chemotherapy (IC): Long-Term Overall Survival (OS) Results from the Phase 3 QUAZAR AML-001 Trial

Abstract

In the QUAZAR AML-001 trial, Oral-AZA significantly prolonged OS vs placebo (median 24.7 vs 14.8 months; P<0.001) in patients with AML in remission after IC and ineligible for transplant. At the primary data cutoff (July 2019) Kaplan-Meier (KM) OS curves for Oral-AZA and placebo converged after ~48 months; 26.5% of patients remained alive and the trial was unblinded. Assess OS at an updated cutoff with additional follow-up. Patients ≥55 years of age, with intermediate- or poor-risk cytogenetics at diagnosis and ECOG PS ≤3, were randomized to Oral-AZA 300mg or placebo once-daily for 14 days/28-day cycle within 4 months of first CR/CRi. After unblinding, Oral-AZA-treated patients could continue treatment in an extension phase. OS was the time from randomization to death, consent withdrawal, or loss to follow-up. Baseline characteristics were compared for long-term (LT) survivors (alive ≥3 years from randomization) versus non-LT survivors. 472 patients were randomized to Oral-AZA (n=238) or placebo (n=234); 39 (16%) Oral-AZA patients entered the extension phase. At the updated data cutoff (Sep 2020), 54 (23%) Oral-AZA patients and 35 (15%) placebo patients were alive; 31 (13%) patients were still receiving Oral-AZA. At a median follow-up of 51.7 months, median OS was unchanged from the primary cutoff (24.7 vs 14.8 months; P=0.0008). However, KM curves showed greater separation at later time-points and did not overlap. KM-estimated 3-year OS rate was 37.4% with Oral-AZA versus 27.9% with placebo (Δ+9.5% [95% CI, 0.9-18.1]). Compared with non-LT survivors, LT survivors (n=140; 83 Oral-AZA, 57 placebo) were more likely to have intermediate-risk cytogenetics (95% vs 82%, respectively) and NPM1mut (45% vs 23%) at AML diagnosis, and less likely to have measurable residual disease (MRD) post-IC (33% vs 52%). Among baseline MRD+ patients, 71% (34/48) of LT survivors became MRD- on study, versus 15% (26/172) of non-LT survivors (P<0.0001). At LT follow-up, median OS was unchanged, but at later time-points the tails of the Oral-AZA and placebo OS curves showed greater separation, indicating sustained LT OS benefit with Oral-AZA. Intermediate-risk cytogenetics and NPM1mut at diagnosis, and absence of post-IC MRD, were associated with LT survival.