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

Author:

Bazarbachi Ali1ORCID,Labopin Myriam2ORCID,Gedde-Dahl Tobias3ORCID,Remenyi Peter4ORCID,Forcade Edouard5ORCID,Kröger Nicolaus6ORCID,Socié Gerard7ORCID,Craddock Charles8ORCID,Bourhis Jean Henri9ORCID,Versluis Jurjen10ORCID,Yakoub-Agha Ibrahim11ORCID,Salmenniemi Urpu12ORCID,El-Cheikh Jean1ORCID,Bug Gesine13ORCID,Esteve Jordi14ORCID,Nagler Arnon15ORCID,Ciceri Fabio16ORCID,Mohty Mohamad17ORCID

Affiliation:

1. 1Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

2. 2EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France.

3. 3Oslo University Hospital, Rikshospitalet, Clinic for Cancer Medicine, Department of Hematology, Section for Stem Cell Transplantation, Oslo, Norway.

4. 4Dél-pesti Centrumkórház–Országos Hematológiai és Infektológiai Intézet, Department of Haematology and Stem Cell Transplant, Albert, Budapest, Hungary.

5. 5Service d'Hématologie Clinique et Thérapie Cellulaire, CHU Bordeaux, Bordeaux, France.

6. 6Department for Stem Cell Transplantation, University Medical Center Hamburg, Hamburg, Germany.

7. 7Hopital St. Louis, Department of Hematology–BMT, Paris, France.

8. 8University Hospital Birmingham NHS Trust, Queen Elizabeth Medical Centre, Edgbaston, Department of Haematology, Birmingham, England.

9. 9Gustave Roussy Cancer Campus, BMT Service, Department of Hematology, Villejuif, France.

10. 10Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Hematology, Rotterdam, the Netherlands.

11. 11CHU de Lille, Univ. Lille, INSERM U1286, Infinite, Lille, France.

12. 12HUCH Comprehensive Cancer Center, Stem Cell Transplantation Unit, Helsinki, Finland.

13. 13Goethe University Frankfurt, Department of Medicine 2, Hematology and Oncology, Frankfurt am Main, Germany.

14. 14Hospital Clínic of Barcelona, IDIBAPS, Barcelona, Spain.

15. 15Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel.

16. 16University Vita-Salute, IRCCS Ospedale San Raffaele, Haematology and BMT, Milano, Italy.

17. 17Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France.

Abstract

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.

Funder

EBMT

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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