Citations 1
Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia
Döhner, Konstanze , Thiede, Christian , Jahn, Nikolaus , Panina, Ekaterina, Gambietz, Agnes, Larson, Richard A. , Prior, Thomas W., Marcucci, Guido , Krauter, Jürgen, Heuser, Michael , Ottone, Tiziana , Nomdedéu, Josep , Mandrekar, Sumithra J. , Klisovic, Rebecca B. , Wei, Andrew H. , Sierra, Jorge , Sanz, Miguel Á. , Brandwein, Joseph , Witte, Théo de , Niederwieser, Dietger , Appelbaum, Frederick R. , Medeiros, Bruno C. , Tallman, Martin S. , Schlenk, Richard F. , Ganser, Arnold , Ehninger, Gerhard , Gathmann, Insa, Benner, Axel , Pallaud, Céline , Stone, Richard M. , Bloomfield, Clara D. , Larson, Richard A , Wei, Andrew H , Jones, Dan M. , Voso, Maria Teresa , Jansen, Joop H. , Serve, Hubert L. , Amadori, Sergio , Döhner, Hartmut
Blood | December 11, 2019 | Volume: 135 | Issue: 5 | Pages: 371-380
Abstract Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (≥0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 NPM1/FLT3-ITD genotypes differed significantly with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after 1 or 2 induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly among ELN risk groups, with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate-, and adverse-risk groups, respectively (P < .001). A multivariate Cox model for OS using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.