Intensive chemotherapy vs venetoclax/hypomethylating agents for patients aged 60 to 75 years with favorable, NPM1-mutated AML.

Patients with nucleophosmin 1 (NPM1)-mutated acute myeloid leukemia (AML) without a FLT3-internal tandem duplication mutation are considered to have favorable-risk disease that may be cured with intensive chemotherapy (7+3; IC) alone. As patients age, the potential for cure without transplant is counterbalanced by morbidity associated with IC. Venetoclax combined with a hypomethylating agent (VEN/HMA) is approved for patients aged ≥75 years or those ineligible for IC, and the regimen is therefore frequently utilized in patients between 60 and 75 years of age. The differences in outcomes between patients with NPM1-mutated, favorable-risk AML who receive IC and VEN/HMA are unknown. We performed a retrospective analysis of patients aged 60 to 75 years with favorable risk, NPM1-mutated AML and compared overall survival (OS) between those treated with IC vs VEN/HMA. We identified 55 patients who met eligibility criteria. Thirty-six patients (65%) received first-line IC, and 19 patients (35%) received first-line VEN/HMA. There was no statistical difference in OS between groups (median survival: IC, 6.2 years; 95% CI, 3.26 years-NR, and VEN/HMA, 4.9 years; 95% CI, 1.1 years-NR). Sixty-day survival in the IC and VEN/HMA cohorts were 97.2% and 100%, respectively. In a univariate analysis, allogeneic hematopoietic cell transplant (alloHCT) in first remission was associated with improved OS (hazard ratio, 0.30; 95% CI, 0.12-0.74), although there were no differences when induction therapy was stratified by alloHCT status. These data suggest that outcomes for patients aged 60 to 75 years with NPM1-mutated AML are comparable between patients initially treated with IC or VEN/HMA.