Outcomes of older patients with NPM1-mutated AML: Current treatments and the promise of venetoclax-based regimens

Abstract

Nucleophosmin-1 mutations (NPM11) occur in ;30% of acute myeloid leukemia (AML) patients. Although typically associated with favorable prognosis, the beneficial impact of NPM11 decreases with increasing age in patients treated with standard intensive chemotherapy (IC) or hypomethylating agents (HMAs). This retrospective analysis compared outcomes of NPM11 AML patients treated with 1 of 3 induction approaches: HMA plus BCL-2 inhibitor venetoclax (VEN), HMA, or IC therapy. Composite complete response (CRc: CR 1 CR with incomplete count recovery) was seen in 96% (27/28), 36% (17/47), and 89% (204/228) of HMA 1 VEN, HMA, and IC patients, respectively (HMA 1 VEN vs HMA, P , .001; HMA 1 VEN vs IC, P 5 .10). Older patients (age .65 years) treated with HMA 1 VEN, HMA, or IC had CR rates of 88%, 28%, and 56%, respectively (HMA 1 VEN vs HMA, P , .001; HMA 1 VEN vs IC, P 5 .01). Significant improvement in overall survival (OS) was seen in patients age .65 years treated with HMA 1 VEN vs HMA (not reached [NR] vs 0.4 years; P , .001) or IC (NR vs 0.93 years; P 5 .001). Older patients treated with HMA 1 VEN had OS of 80% after median 1-year follow-up, with estimated 2-year OS of 70%. In the multivariable Cox model analysis, HMA 1 VEN was associated with a 69% lower risk of death compared with IC (hazard ratio, 0.31; 95% confidence interval, 0.12-0.83; type I error-adjusted P 5 .038). HMA 1 VEN combinations demonstrated impressive results compared with traditional standard-of-care regimens in older patients with NPM11 AML.