Clinical outcomes associated with NPM1 mutations in newly diagnosed acute myeloid leukemia

Nucleophosmin 1-mutated (NPM1mt) acute myeloid leukemia (AML) is associated with a relatively favorable prognosis though long-term outcomes remain suboptimal without clear predictors identified by therapy.

In a retrospective analysis, the authors identified 396 patients (18%) with newly diagnosed (ND) NPM1mt AML treated at The University of Texas MD Anderson Cancer Center and analyzed their outcomes. Using a Cox regression model, they analyzed predictors of survival in newly diagnosed NPM1mt AML across various therapies.

Those treated with high intensity chemotherapy had a median overall survival (OS) of 84.7 months with a 5-year rate of 53% (95% CI, 44%-61%) whereas those treated with a combination of a hypomethylating agent (HMA) and venetoclax had a median OS of 23.3 months with a 5-year rate of 19% (95% CI, 5%-39%). The combination of cladribine, low-dose cytarabine, and venetoclax alternating with azacitidine and venetoclax yielded better survival compared with HMA and venetoclax in an age-matched analysis (5-year OS rate of 74% vs. 24%) (p = .048).

Among patients with NPM1mt treated with high-intensity chemotherapy, older age, a poor performance status, and presence of a FLT3-ITD mutation or extramedullary disease predicted a worse overall survival. For patients treated with a hypomethylating agent and venetoclax, older age was the only predictor of worse long-term outcomes. These findings can be used for risk-stratification of newly diagnosed NPM1mt AML and provide benchmarks of response and survival for this subtype.