Oral azacitidine confers survival benefits in patients with acute myeloid leukemia (AML) in first complete remission (CR) after intensive chemotherapy regardless of favorable or adverse prognostic AML features, according to research published in Blood.

The findings come from the randomized, placebo-controlled, phase 3 QUAZAR AML-001 trial (ClinicalTrials.gov identifier: NCT01757535). Researchers evaluated oral azacitidine vs placebo in patients aged ≥55 years of age with newly diagnosed de novo or secondary AML (WHO 2008 classification) and intermediate- or poor-risk cytogenetic findings at diagnosis (NCCN 2011 criteria) in first CR or CR with incomplete blood recovery (CRi) after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation.

Within 4 months (±7 days) of achieving first CR or CRi, patients were randomly assigned (1:1) to receive oral azacitidine (300 mg) or placebo for 14 days per 28-day cycle. The primary endpoint was OS, and the secondary endpoint was RFS. The investigators assessed patient subgroups according to their NPM1 and FLT3 mutational status at AML diagnosis and measurable residual disease (MRD) status following intensive chemotherapy.

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A total of 472 patients were included in the study. Mutational data were available for 99.4% of patients. The team found NPM1 mutations (NPM1mut) in 29.2%, FLT3 mutations (FLT3mut; with internal tandem duplications [ITD], tyrosine kinase domain mutations [TKDmut], or both) in 14.1%, and NPM1mut and FLT3-ITD in 6.4% of patients.

Among patients in the NPM1mut subgroup, the researchers found oral azacitidine improved OS by 37% (47.2 vs 15.9 months; hazard ratio [HR], 0.63; 95% CI, 0.41-0.98; P =.038) and RFS by 45% (23.2 vs 6.9 months; HR, 0.55; 95% CI, 0.35-0.84; P =.005) compared with placebo. The median OS with oral azacitidine compared with placebo was 48.6 vs 31.4 months for patients with NPM1mut without MRD and 46.1 vs 10.0 months for patients with NPM1mut with MRD.

Among patients in the FLT3mut subgroup, the researchers found oral azacitidine improved OS by 37% (median, 24.7 vs 15.2 months; HR, 0.63; 95% CI, 0.35-1.12; P =.013) and RFS by 49% (median, 23.1 vs 4.6 months; HR, 0.51; 95% CI, 0.27-0.95; P =.032) compared with placebo. The median OS with oral azacitidine compared with placebo was 28.2 vs 16.2 months for patients with FLT3mut without MRD and 24.0 vs 8.0 months for patients with FLT3mut with MRD.

Using multivariate analyses, the investigators demonstrated treatment with oral azacitidine (vs placebo) was an independent prognostic factor of improved OS

(P =.004) and RFS (P <.001) after controlling for NPM1 mutational status, FLT3 mutational status, cytogenetic risk at AML diagnosis, and post-intensive chemotherapy MRD status at baseline.

“These data suggest that [oral azacitidine] maintenance therapy can benefit substantially patients with AML in remission who are not candidates for hematopoietic stem cell transplantation and who have poor prognostic disease features (FLT3mut at diagnosis, MRD after [intensive chemotherapy]) and further can improve survival outcomes for patients with more favorable prognostic disease characteristics (NPM1mut at diagnosis, no MRD after [intensive chemotherapy]) compared with placebo,” concluded the researchers.

Limitations of the study included locally conducted mutational assessments at the time of patient diagnosis coupled with rapidly evolving methodologic advancements in genetic testing and understanding of the genetic landscape of AML during the study enrollment period and inclusion of only patients who achieved remission with intensive chemotherapy.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Döhner H, Wei AH, Roboz GJ, et al. Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacitidine. Blood. 2022;140(15):1674-1685. doi:10.1182/blood.2022016293