Abstract
Background: NPM1 is commonly mutated in AML and represents a distinct entity under the WHO 2016 classification. It is one of the few mutations that can potentially support favorable risk by ELN 2017. Mutations that are highly specific for secondary AML (sMT) including SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2 (Lindsley et al.) have been shown to confer poor prognosis. Objective: In this study, we explore the outcomes in patients with NPM1 mutated AML. Methods: This was a retrospective study of NPM1 AML mutated patients who were treated at the Moffitt Cancer Center from 2013-2020. Only those with NPM1 mutations and NGS performed at diagnosis were included in the study (n=115). Kaplan-Meier, univariate, and multivariate analyses were performed. Results: Of the 115 patients (54M/85F, median age 61 at diagnosis), majority had de novo AML (83.5%). Over half of them had favorable risk (55.7%), followed by intermediate risk (35.6%), and adverse risk (8.7%). Almost 80% had normal cytogenetics at the time of diagnosis. Common co-mutations included DNMT3A (47.8%), FLT3-ITD (39.1%), TET2 (20%), FLT3-TKD (18.3%), IDH1 (18.3%), and IDH2(16.5%). sMT occurred in 16.5% of the entire cohort and 17.2% among those with ELN favorable risk. Patients with sMT have a significantly lower rates of relapse freedom after CR/CRi (26.3% vs 52.1%, p=0.047). Numerically, higher rates of relapse after CR/CRi (47.4% vs 34.4%, p=0.301) and higher rates of never achieving CR/CRi (26.3% vs 13.5%, p=0.175). Among favorable risk, OS was 14. 7 months for sMT vs not reached for those without sMT (p Conclusions: Our findings suggest NPM1 mutated AML patients with sMT have significantly worse prognosis despite being classified as favorable risk by ELN 2017 at diagnosis. This may have treatment implications in the need for and/or timing of HCT. Further studies and larger datasets are needed to confirm these observations.
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