Differences in prognostic value of FLT3 and NPM1 mutations in older and younger patient populations with acute myeloid leukemia

The prognostic value of nucleophosmin-1 (NPM1) and fms-like tyrosine kinase 3 (FLT3) mutations has been well-established in adult patients but is less clear in geriatric patients. This retrospective cohort study assessed adult patients with acute myeloid leukemia (AML) who received FLT3 and/or NPM1 testing treated at any Veterans Health Administration (VHA) facility or at Vanderbilt University Medical Center (VUMC) between January 2006 and December 2016. The primary analysis compared time to all-cause death among patients with AML based on FLT3 and NPM1 mutation status, age (<65 years, [&ge;]65 years), and cytogenetic risk group (unfavorable, intermediate/normal, favorable). The study population (n=766) (mean age 59.71 {+/-} 16.6 years, 45.96% [&ge;]65 years) had a mutation rate of 19.8% for FLT3 and 22.1% for NPM1. Age was a significant factor in overall survival (median OS: 24.28 vs. 8.18 months, p<0.001), as was cytogenetic risk status (median OS: favorable group not reached, intermediate/normal 17.61m vs. unfavorable 6.77m, p<0.001). The most favorable prognostic group (FLT3-/NPM1+) among older patients showed worse OS (15.21 months) than did the poor prognostic group (NPM1-/FLT3-) among younger patients (18.43 months). Among the older cohort, FLT3 and NPM1 mutation status, favorable karyotype, and CCI were not identified as prognostic factors. In the full cohort, using Cox proportional hazard regression and LASSO analyses for age, FLT3 and NPM1 mutation status, cytogenetic risk group, treatment site, race, primary payor, and Charleston Comorbidity Index (CCI), age (HR 65y vs 35y/=2.44, 95% CI 1.61-3.68, p<0.001) was the strongest risk factor in AML.