Prognostic Significance of Secondary-Type Mutations in NPM1-Mutated Acute Myeloid Leukemia

NPM1 is among the most frequently mutated genes in acute myeloid leukemia (AML), and NPM1-mutated AML is generally associated with a favorable prognosis. However, substantial prognostic heterogeneity exists within this population. The prognostic significance of secondary-type mutations (STMs) in NPM1-mutated AML remains controversial. In this retrospective study of 179 patients with NPM1-mutated AML, the prognostic effects of age, common comutations, and STMs were evaluated. Multivariate analysis revealed that age ≥ 60 years and the presence of FLT3-ITD mutations were independently associated with poor overall survival (OS). Patients with NPM1/FLT3-ITD/DNMT3A triple mutations had the shortest median OS among the molecular subgroups examined. The treatment response did not differ significantly between STM-positive and STM-negative patients. No statistically significant association between STM status and OS was observed in the overall cohort or in exploratory subgroup analyses stratified by ELN 2022 risk category and age. Sensitivity analyses accounting for stem cell transplantation and untreated patients yielded similar results. Given the limited number of STM-positive patients, larger studies are needed to further clarify the prognostic significance of STMs in NPM1-mutated AML.