Outcome of Patients With IDH-Mutated AML Following Allogeneic Stem Cell Transplantation-A Retrospective Analysis on Behalf of the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy, DRST

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Thomas Schroeder - , University Hospital Essen (Author)
  • Sarah Flossdorf - , University Hospital Essen, German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST) (Author)
  • Claudia Schuh - , German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST) (Author)
  • Caroline Pabst - , University Hospital Heidelberg (Author)
  • Michael Stadler - , Hannover Medical School (MHH) (Author)
  • Johannes Schetelig - , Department of Internal Medicine I (Author)
  • Claudia Wehr - , University Medical Center Freiburg (Author)
  • Matthias Stelljes - , University Hospital Münster (Author)
  • Elisa Sala - , Ulm University Medical Center (Author)
  • Andreas Burchert - , University Hospital Gießen and Marburg (Author)
  • Julia Winkler - , University Hospital at the Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • H Christian Reinhardt - , University Hospital Essen (Author)
  • Nicolaus Kröger - , German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST), University Hospital Hamburg Eppendorf (Author)
  • Katharina Fleischhauer - , German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST), University Hospital Essen (Author)
  • Christina Rautenberg - , University Hospital Essen (Author)

Abstract

Mutations in isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are found in 15% to 20% of patients with acute myeloid leukemia (AML). IDH inhibitors have been introduced as targeted treatment and are currently under investigation as maintenance therapy after allogeneic transplantation (allo-SCT). Since reports about the outcome of IDH1- and IDH2-mutated (IDHmut) AML after allo-SCT are limited, we retrospectively analyzed 356 IDH-mutated AML patients (IDH1 40%, IDH2 60%). Ten patients (4%) had received an IDH inhibitor prior transplantation, but none had received maintenance with IDH inhibitors. After a median follow-up of 24 months 3-year probabilities of overall (OS) and event-free (EFS) survival, relapse and nonrelapse mortality (NRM) for the entire cohort were 73%, 60%, 27% and 13% respectively. While 3-year OS (78% versus 70%), EFS (56% versus 63%) and NRM (10% versus 14%) rates were similar for IDH1mut and IDH2mut patients, relapse incidence was numerically higher in IDH1mut patients (34% versus 24%) and landmark analysis suggested a continuous rise of relapse incidence preferentially in IDH1mut AML also beyond the first year. Concordantly, IDH2 mutation was associated with superior EFS and by trend with lower relapse incidence. The strongest risk factor for adverse outcomes, however, was AML not in CR. This analysis provides benchmarks for interpretation of results emerging from post-transplant maintenance trials in IDHmut AML and suggest that maintenance strategies may further optimize the promising outcome in this molecularly defined subgroup by reducing relapse risk, especially for patients whose AML is not in remission at time of alloHCT.

Details

Original languageEnglish
Pages (from-to)303.e1-303.e9
JournalTransplantation and cellular therapy
Volume31
Issue number5
Publication statusPublished - May 2025
Peer-reviewedYes

External IDs

Scopus 105000929383

Keywords

Keywords

  • Adolescent, Adult, Aged, Female, Germany, Hematopoietic Stem Cell Transplantation/methods, Humans, Isocitrate Dehydrogenase/genetics, Leukemia, Myeloid, Acute/genetics, Male, Middle Aged, Mutation, Registries, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Young Adult, AML, Relapse, Allogeneic transplantation, IDH mutation, Maintenance