The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting

Gunnar Juliusson, Martin Jädersten, Stefan Deneberg, Sören Lehmann, Lars Möllgård, Lovisa Wennström, Petar Antunovic, Jörg Cammenga, Fryderyk Lorenz, Emma Ölander, Vladimir Lj Lazarevic, Martin Höglund, Gunnar Juliusson, Martin Jädersten, Stefan Deneberg, Sören Lehmann, Lars Möllgård, Lovisa Wennström, Petar Antunovic, Jörg Cammenga, Fryderyk Lorenz, Emma Ölander, Vladimir Lj Lazarevic, Martin Höglund

Abstract

In acute myeloid leukemia (AML) FLT3 internal tandem duplication (ITD) and nucleophosmin 1 (NPM1) mutations provide prognostic information with clinical relevance through choice of treatment, but the effect of age and sex on these molecular markers has not been evaluated. The Swedish AML Registry contains data on FLT3-ITD and NPM1 mutations dating to 2007, and 1570 adult patients younger than 75 years, excluding acute promyelocytic leukemia, had molecular results reported. Females more often had FLT3ITD and/or NPM1mut (FLT3ITD: female, 29%; male, 22% [P = .0015]; NPM1mut: female, 36%; male, 27% [P = .0001]), and more males were double negative (female, 53%; male, 64%; P < .0001). Patients with FLT3ITD were younger than those without (59 vs 62 years; P = .023), in contrast to patients with NPM1mut (62 vs 60 years; P = .059). Interestingly, their prognostic effect had a strong dependence on age: FLT3ITD indicated poor survival in younger patients (<60 years; P = .00003), but had no effect in older patients (60-74 years; P = .5), whereas NPM1mut indicated better survival in older patients (P = .00002), but not in younger patients (P = .95). In FLT3ITD/NPM1mut patients, the survival was less dependent on age than in the other molecular subsets. These findings are likely to have clinical relevance for risk grouping, study design, and choice of therapy.