Maintenance with oral azacitidine confers survival benefits in patients with acute myeloid leukemia (AML) regardless of NPM1 or FLT3 mutational status, cytogenetic risk, or measurable residual disease (MRD) status after intensive chemotherapy, according to research published in Blood.

These findings come from the randomized, phase 3 QUAZAR AML-001 trial ( identifier: NCT01757535). Researchers evaluated maintenance with oral azacitidine vs placebo in patients 55 years of age or older with de novo or secondary AML and intermediate- or poor-risk cytogenetics at diagnosis.

Patients were in first complete remission (CR) or CR with incomplete blood recovery (CRi) after induction chemotherapy, with or without subsequent consolidation, and were not candidates for hematopoietic stem cell transplant.

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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 overall survival (OS), and the secondary endpoint was relapse-free survival (RFS). The investigators assessed patient subgroups according to their NPM1 and FLT3 mutational status at AML diagnosis and MRD status following chemotherapy.

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

Among patients in the NPM1mut subgroup, azacitidine improved OS by 37% and RFS by 45%. The median OS was 47.2 months with azacitidine and 15.9 months with placebo (hazard ratio [HR], 0.63; 95% CI, 0.41-0.98; P =.038). The median RFS was 23.2 months and 6.9 months, respectively (HR, 0.55; 95% CI, 0.35-0.84; P =.005).

For patients with NPM1mut without MRD, the median OS was 48.6 months with azacitidine and 31.4 months with placebo. For patients with NPM1mut with MRD, the median OS was 46.1 months and 10.0 months, respectively.

Among patients in the FLT3mut subgroup, azacitidine improved OS by 37% and RFS by 49%. The median OS was 24.7 months with azacitidine and 15.2 months with placebo (HR, 0.63; 95% CI, 0.35-1.12; P =.013). The median RFS was 23.1 months and 4.6 months, respectively (HR, 0.51; 95% CI, 0.27-0.95; P =.032).

For patients with FLT3mut without MRD, the median OS was 28.2 months with azacitidine and 16.2 months with placebo. For patients with FLT3mut with MRD, the median OS was 24.0 months and 8.0 months, respectively.

In a multivariate analysis, azacitidine was an independent predictor 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 [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,” the researchers concluded.

Disclosures: This research was sponsored by Celgene. Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of 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

This article originally appeared on Hematology Advisor