Improved post-transplant outcomes in recent years for AML patients with FLT3-ITD and wild-type NPM1: a report from the EBMT acute leukemia working party

Abstract

Purpose: Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended in first complete remission (CR1) in acute myeloid leukemia (AML) patients harboring FLT3 internal tandem duplication (FLT3-ITD). We assessed changes over time in transplant characteristics and outcomes in AML patients aged 60 years and younger with a FLT3 ITD. Experimental Design: We identified 1827 adult AML patients (median age 49 years, range 18-60) with FLT3 ITD and intermediate karyotype, allografted between 2012 and 2021 in CR1. Results: NPM1 was mutated in 72% of patients. We compared changes over time in 688 patients transplanted between 2012 and 2016, and 1139 patients transplanted between 2017 and 2021. For patients with wild-type NPM1, the 2-year leukemia free survival (LFS) and overall survival (OS) significantly improved over time from 54% to 64% (hazard ratio [HR] =0.67; p=0.011) and from 63% to 71% (HR=0.66; p=0.021), respectively. Allo-HCT in recent years significantly reduced the cumulative incidence of relapse (CIR). For patients with NPM1 mutation, no significant changes over time were noted. Conclusions: In AML patients with FLT3 ITDand wild-type NPM1, we noticed a significant decrease over time in the CIR and improvement of LFS and OS, likely reflecting the efficacy of FLT-3 inhibitors, including when used as post-transplant maintenance, in this high-risk setting. On the contrary, no significant change over time was noticed in outcomes of patients harboring a FLT3 and NPM1 mutation.