The oral azacitidine (Oral-AZA) was tested in patients with acute myeloid leukemia (AML) in the first remission following intensive chemotherapy (IC) who were not candidates for hematopoietic stem cell transplantation in the randomized, placebo-controlled, phase 3 QUAZAR AML-001 trial.

For 14 days per 28-day cycle, eligible patients were randomly assigned 1:1 to receive 300 mg of oral-AZA or a placebo. For a study, researchers assessed whether the existence of post-IC measurable residual disease (MRD) affected relapse-free survival (RFS) and overall survival (OS) in patient subgroups defined by NPM1 and FLT3 mutational status at AML diagnosis. Gene mutations upon diagnosis were gathered from patient case report forms, and multiparameter flow cytometry was used to centrally assess MRD.

In total, 469 of the 472 randomly selected patients (99.4%) had mutational data available; of these, 137 patients (29.2%) had NPM1 mutations (NPM13mut), 66 patients (14.1%), FLT3 mutations (FLT3mut); with internal tandem duplications [ITD], tyrosine kinase domain mutations [TKDmut], or both), and 30 patients (6.4%) had  NPM13mut and FLT3-ITD at diagnosis. In NPM13mut patients, OS and RFS were improved with Oral-AZA by 37% (hazard ratio [HR], 0.63; 95% CI, 0.41-0.98) and 45% (HR, 0.55; 95% CI, 0.35-0.84), respectively, vs. placebo. With or without MRD (48.6 months vs. 31.4 months with placebo) and with or without MRD (46.1 months vs. 10.0 months with placebo) after IC, patients with NPM13mut saw a numerical improvement in median OS with oral-AZA. When compared to placebo, oral-AZA significantly improved OS and RFS in FLT33mut patient populations by 37% (HR, 0.63; 95% CI, 0.35-1.12) and 49% (HR, 0.51; 95% CI, 0.27-0.95), respectively. For patients with FLT33mut and without MRD, the median OS with oral-AZA compared to placebo was 28.2 months, while for those with FLT33mut with MRD, it was 24.0 months.

Oral-AZA substantially increased survival in multivariate analysis, regardless of the presence of NPM1 or FLT3 mutations, cytogenetic risk, or post-IC MRD status.