Prognostic Impact of NPM1/FLT3-ITDgenotypes from Randomized Patients with Acute Myeloid Leukemia (AML) Treated within the International Ratify Study

Background:Patients (pts) with AML harboring FLT3-ITD mutations have poor outcomes. The higher relapse rate and inferior overall survival (OS) largely depend on the ITD mutant to wild-type (wt) allelic ratio. Furthermore, there is a strong gene-gene interaction between NPM1mutation (NPM1mut) and FLT3-ITD. Consequently, the 2017 European LeukemiaNet (ELN) has included defined NPM1/FLT3-ITD genotypes for risk categorization. In the recent phase III RATIFY trial [NCT00651261; Stone et al., NEJM 2017] the addition of the multi-targeted kinase inhibitor midostaurin (M) to standard chemotherapy significantly prolonged OS and event-free survival (EFS) in pts with newly diagnosed AML and FLT3mutation. Here, we evaluated the prognostic impact in a post-hoc analysis of the NPM1/FLT3-ITD genotypes as defined by the 2017 ELN from randomized pts treated within the RATIFY trial.