Acute Myeloid Leukemia Coverage From Every Angle

Impact of NPM1 and FLT3 Mutations on Prognosis in Patients With AML in Remission

By: Vanessa A. Carter, BS
Posted: Friday, January 7, 2022

Hartmut Döhner, MD, of Ulm University Hospital, Germany, and colleagues assessed the prognostic impact of NPM1 and FLT3 mutations and the presence of measurable residual disease (MRD) for patients with acute myeloid leukemia (AML) in first remission. Presented during the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 804), outcomes from the phase III QUAZAR-001 study suggest that oral azacitidine prolonged overall and relapse-free survival in individuals with these characteristics.

This trial enrolled 472 patients with AML who had intermediate- or poor-risk cytogenetics. Participants were randomly assigned 1:1 to receive oral azacitidine or placebo within 4 months of achieving complete response after intensive chemotherapy.

Mutational data were available for 469 patients, and 463 were evaluable for MRD. An NPM1 mutation was observed in 66 patients given azacitidine and 71 given placebo; this mutation was significantly associated with negative MRD at baseline (P = .0178). Additionally, overall survival appeared to be improved in those with this aberration receiving azacitidine versus a placebo (48.6 vs. 26.2 months; P < .0001).

The median overall survival for patients with NPM1 mutations given placebo appeared to be influenced by MRD status, as patients who had MRD negativity were found to have longer survival (26.2 vs. 10.3 months). Additionally, the median relapse-free survival for patients with NPM1 mutations and negative MRD status in both the azacitidine and placebo groups was 24.9 versus 9.9 months, respectively; patients with MRD positivity had survival of 19.4 versus 4.6 months.

Approximately 14.1% of participants had FLT3 alterations at diagnosis. The majority of patients with aberrations had an NPM1 mutation but not FLT3 (n = 107), 30 had both mutations, and 16 had an FLT3 alteration. The median overall survival was not found to be significantly impacted by FLT3 mutations, although the risk of death was reduced by 46% with azacitidine. Of note, NPM1 status, FLT3 status, MRD status, and cytogenetic risk were each significantly predictive of overall survival.

Disclosure: For full disclosures of the study authors, visit

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