FLT3

Haplo-SCT may be an effective therapy option for AML patients harboring FLT3-ITD mutation

It is well-known that fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation adversely impacts acute myeloid leukemia (AML) patient outcomes. The preponderance of evidence suggests that allogeneic stem cell transplantation (allo-SCT) in first remission is probably the best treatment option for this patient population. On the other hand, it remains unknown whether FLT3-ITD mutation has any impact on survival after haploidentical stem cell transplantation (haplo-SCT).

Jonathan Canaani from Chaim Sheba Medical Center, Hematology Division, Tel Aviv University, Tel-Hashomer, IL, and colleagues from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) retrospectively analyzed AML patients undergoing T-cell replete haplo-SCT in first complete remission (CR1) with an aim to determine the prognostic significance of FLT3-ITD after haplo-SCT. The findings were published ahead of print in the American Journal of Hematology.

Using the registry of the ALWP of the EBMT, Canaani et al. identified 293 adult de novo AML patients who underwent a first T-cell replete related halpo-SCT between 2005-2016. Of these patients, 91 were FLT3-ITD mutated and 202 were FLT3 wild-type (FLT3WT). Compared to FLT3WT patients, FLT3-ITD mutated AML patients were more likely to have Medical Research Council (MRC) intermediate risk cytogenetics and concomitant NPM1 mutation.

Key findings:
  • Clinical outcomes in the FLT3-ITD mutated and FLT3wt groups respectively
    • 2-year relapse incidence: 24% vs 14%, P = 0.1
    • 2-year leukemia-free survival (LFS): 55% vs 63%, P = 0.49
    • 2-year non-relapse mortality: 20% vs 22%, P = 0.62
    • Acute and chronic graft versus host disease (GvHD), and GvHD-free/relapse-free survival: 49% vs 50%, P = 0.79
    • 2-year overall survival (OS): 65% vs 67%, P = 0.88

In summary, harboring FLT3-ITD mutation did not significantly influence the clinical outcomes of patients who underwent T-cell replete haplo-SCT.  A subset analysis of patients with intermediate-risk cytogenetics also confirmed the absence of a prognostic impact for FLT3-ITD mutation. According to the authors, the findings of this study “supports the emerging and substantial role for haplo-SCT in FLT3-ITD AML patients” which may be a preferred “therapeutic modality for this specific high-risk subset of patients”.

Canaani et al. concluded by stating that “haploidentical transplantation for AML patients in first remission is a feasible option with very good outcomes” and thus suggested that halpo-SCT “should be performed without delay as outcomes beyond first remission are very poor”.  

References
  1. Canaani J. et al. T-cell replete haploidentical stem cell transplantation attenuates the prognostic impact of FLT3-ITD in acute myeloid leukemia. A report from the Acute Leukemia Working Party of the EBMT. Am J Hematol. 2018 Mar 2. DOI: 10.1002/ajh.25082.
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