Intensive Chemotherapy vs. Venetoclax/Hypomethylating Agents for Patients Aged 60-75 with Favorable, NPM1-mutated AML Open Access

• Outcomes of patients aged 60-75 years with favorable-risk, NPM1 mutated AML are similar between intensive and less intense regimens.

• Patients who underwent alloHCT had excellent outcomes, regardless of their first line treatment regimen.

Patients with NPM1-mutated AML in the absence of a FLT3-ITD 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 or those ineligible for intensive chemotherapy, 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 60-75 with favorable risk, NPM1-mutated AML and compared overall survival (OS) between those treated with intensive chemotherapy to those who received 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 overall survival between the groups (median survival: IC 6.2 years, 95% CI: 3.26 years – not reached, and VEN/HMA 4.9 years, 95% CI: 1.1 years – not reached). Sixty-day survival in the IC and VEN/HMA cohorts were 97.2% and 100% respectively. In a univariate analysis, alloHCT in first remission was associated with improved OS (HR = 0.30, 95% CI: 0.12-0.74), though there were no differences when induction therapy was stratified by alloHCT status. These data suggest that outcomes for patients aged 60-75 with NPM1-mutated AML are comparable between patients initially treated with IC or VEN/HMA.