FLT3

EBMT 2018 | Post-transplant maintenance with sorafenib improves survival of FLT3-mutated AML patients

Mutations in the fms-like tyrosine kinase 3 (FLT3) gene represent one of the most commonly encountered, and clinically challenging, classes of acute myeloid leukemia (AML) mutations and it is expressed in approximately 30% of patients. Allogenic hematopoietic stem cell transplantation (allo-HSCT) is recommended for FLT3-mutated AML patients in first complete remission (CR1). However, the long-term outcomes in this group of patients are still poor.

Ali Bazarbachi, from the American University of Beirut Medical Center, Beirut, LB, and colleagues, evaluated the influence of patient, disease and transplant characteristics on the post-transplant outcomes of FLT3-mutated AML patients. The data from this study was presented at the 44th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Lisbon, Portugal.

Bazarbachi and colleagues identified from EBMT centers, 462 adult FLT3-mutated AML patients (median age at transplant = 50 years) who underwent allo-HSCT either from a matched-related (40%), matched-unrelated (49%) or haploidentical (11%) donor between 2010–2015. Patients were transplanted either in CR1 (71.5%), second CR (CR2, 10.5%), or with active disease (18%). Sorafenib was administered either at pre-transplant during induction (n = 9), during consolidation (n = 10), salvage therapy (n = 8) or post-transplant maintenance (n = 28). The median follow-up time for surviving patients was 39 months (range 1–87).

Key findings:
  • 2-year cumulative incidence of:
    • Grade II–IV acute graft versus host disease (GvHD): 26.3%
    • Chronic GvHD: 34.2%
    • Extensive GvHD: 16%
    • Relapse: 33.9%
    • Non-relapse mortality (NRM): 15%
    • Leukemia-free survival (LFS): 51%
    • Overall survival (OS): 59%
    • GvHD relapse-free survival (GRFS): 38.4%
  • NPM1 mutation, transplantation in CR1, in vivo T cell depletion, and sorafenib maintenance associated significantly with an improved OS
  • NPM1 mutation (HR = 0.66, P = 0.002), the use of a haploidentical donor compared to matched sibling donors (HR = 0.61, P = 0.04), in vivo T cell depletion (HR = 0.55, P = 0.00001), and sorafenib maintenance (HR = 0.44, P = 0.02) significantly associated with an improved GRFS

In summary, post-transplant maintenance significantly improved the OS and GFRS of FLT3-mutated AML patients undergoing allo-HSCT. Bazarbachi et al. concluded by suggesting that sorafenib post-transplant maintenance should be “considered as the standard of care” for FLT3 mutated AML patients.

References
  1. Bazarbachi A. et al. Influence of patient, disease and transplant characteristics in post transplant outcomes in FLT3 mutated AML.: A report from the EBMT Acute Leukemia Working Party. Oral abstract #OS7-6. 2018 European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting, Lisbon, PT.
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