Improved Posttransplant Outcomes in Recent Years for AML Patients with FLT3-ITD and Wild-type NPM1: A Report from the EBMT Acute Leukemia Working Party

Clin Cancer Res. 2023 Nov 1;29(21):4441-4448. doi: 10.1158/1078-0432.CCR-23-0954.

Abstract

Purpose: Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended in first complete remission (CR1) in patients with acute myeloid leukemia (AML) harboring FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD). We assessed changes over time in transplant characteristics and outcomes in patients with AML age 60 years and younger with a FLT3-ITD.

Experimental design: We identified 1,827 adult patients with AML (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 1,139 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% (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 patients with AML with FLT3-ITD and 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 posttransplant 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.

MeSH terms

  • Adolescent
  • Adult
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / therapy
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Prognosis
  • Retrospective Studies
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Nuclear Proteins
  • Nucleophosmin
  • fms-Like Tyrosine Kinase 3
  • FLT3 protein, human