FLT3

Allo-SCT in older FLT3/ITD AML patients

Mutation in the Internal Tandem Duplication of the FMS-Like Tyrosine Kinase 3 (FLT3-ITD) gene is associated with poor survival outcomes and high relapse rates in Acute Myeloid Leukemia (AML) patients. Previous studies have demonstrated Allogeneic Stem Cell Transplantation (allo-SCT) in First Complete Remission (CR1) to be a curative option for younger patients below the age of 60 with AML. However, in older patients, there is a paucity of studies that investigated this effect, hence the rationale for this study.

Xavier Poiré from the Cliniques Universitaires Saint-Luc, Brussels, Belgium, and colleagues on behalf of the Acute Leukemia Working Party (ALWP) of the European Society Of Blood And Marrow Transplantation (EBMT), retrospectively analyzed the potential benefit of  allo-SCT in patients  ≥ 60 years with de novo  FLT3-ITD AML. The results of the study were published in a recent edition of Haematologica.

Using the EBMT registry, the authors identified 291 intermediate-risk FLT3-ITD de novo AML patients (median age = 63.7 years) who underwent allo-SCT either from a related or unrelated donor between January 2000 and December 2015. Patients were transplanted either in CR1 (n = 212), Second Complete Remission (CR2, n = 37) or had Active Disease (AD) at the time of transplantation (n = 42). The endpoints of the study were Leukemia-Free Survival (LFS), Cumulative Incidence of Relapse (CIR), Non-Relapse Mortality (NRM), and GvHD-free/relapse free survival (GRFS) and Overall Survival (OS).

Key findings:
  • Survival
    • 2-year LFS for all patient was 44.3%
      • 2-year LFS in patients in CR1, CR2 and AD at the time of transplantation were 55.9%, 21.6% and 9.5% respectively, P < 0.001
    • 2-year OS in all patients was 46.7%
      • 2-year OS in patients in CR1, CR2 and AD at the time of transplantation were 58.7%, 28.8% and 9.5% respectively, P < 0.001
    • 2-year GRFS in all patients was 32.3%
      • 2-year GFRS in patients in CR1, CR2 and AD at the time of transplantation were 41.7%, 18.1% and 2.4% respectively, P < 0.001
    • NRM
      • 2-year cumulative incidence of NRM for all patients was 20%
      • AD at the time of SCT was significantly associated with increased NRM, P = 0.01
    • CIR
      • 2-year CIR in all patients was 35.4%
        • 2-year CIR in patients in CR1, CR2 and had AD at the time of transplantation were 26.1%, 56.8% and 61.9% respectively, P < 0.001

 

The authors noted that their study demonstrated that disease status at transplantation correlated with LFS, GRFS and OS. Thus, they recommended SCT as a consolidation strategy for fit ≥ 60-year-old patients with FLT3-ITD AML in CR1.

The authors stated that allo-SCT outcomes remain superior for older FLT3/ITD AML patients if the transplantation is being performed in CR1, similarly to previous observations in younger patients. They further concluded that “they do not recommend to postpone SCT till relapse in view of the inferior results observed when SCT is performed in CR2 and beyond.”. However, “they strongly recommend to offer SCT in early disease phase for every eligible patient with AML and FLT3-ITD as the best consolidation strategy”.

References
  1. Poiré X. et al. Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3-ITD; a study from the Acute Leukemia Working Party (ALWP) of the European Society of Blood and Marrow Transplantation (EBMT). Haematologica. 2017 Dec 14. DOI: 10.3324/haematol.2017.178251. [Epub ahead of print].
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