LAUSR

The randomized, placebo-controlled, phase 3 QUAZAR AML-001 trial (NCT01757535) evaluated oral azacitidine (Oral-AZA) in patients with AML in first remission after intensive chemotherapy (IC) who were not candidates for hematopoietic stem cell transplant. Eligible patients were randomized 1:1 to Oral-AZA 300 mg or placebo for 14 days/28-day cycle. We evaluated relapse-free (RFS) and overall (OS) survival in patient subgroups defined by NPM1 and FLT3 mutational status at AML diagnosis, and whether survival outcomes in these subgroups were influenced by presence of post-IC measurable residual disease (MRD). Gene mutations at diagnosis were collected from patient case report forms; MRD was determined centrally by multiparameter flow cytometry. Overall, 469 of 472 randomized patients (99.4%) had available mutational data; 137 patients (29.2%) had NPM1mut, 66 (14.1%) had FLT3mut (-ITD and/or -TKDmut), and 30 (6.4%) had NPM1mut/FLT3-ITD at diagnosis. Among patients with NPM1mut, OS and RFS were improved with Oral-AZA by 37% (HR 0.63 [95%CI 0.41-0.98]) and 45% (0.55 [0.35-0.84]), respectively, vs placebo. Median OS was numerically improved with Oral-AZA among NPM1mut patients whether MRD- (48.6 months, vs 31.4 months with placebo) or MRD+ (46.1 vs 10.0 months) post-IC. Among patients with FLT3mut, Oral-AZA improved OS and RFS by 37% (HR 0.63 [95%CI 0.35-1.12]) and 49% (0.51 [0.27-0.95]), respectively, vs placebo. Median OS with Oral-AZA vs placebo was 28.2 vs 16.2 months, respectively, for FLT3mut/MRD- patients, and 24.0 vs 8.0 months for FLT3mut/MRD+ patients. In multivariate analyses, Oral-AZA significantly improved survival independent of NPM1 or FLT3 mutational status, cytogenetic risk, or post-IC MRD status.