Patients With Relapsed or Refractory FLT3m+ AML Are Especially Challenging to Treat1,2

In AML, the prognosis for patients with relapsed or refractory disease is poor1
  • Mutations in FLT3 are the most common mutations in AML, with 30% positive for FLT3-ITD and 7% positive for FLT3-TKD3
    • FLT3-ITD mutations are associated with higher risk of relapse and shorter OS compared with wild-type FLT34,5
  • The impact of FLT3-TKD mutations on prognosis is less clear.6 Some studies have shown FLT3-TKD mutations:
    • Showed no prognostic significance6
    • May depend on other genetic aberrations to have an impact on prognosis7
    • May be associated with shorter DFS and OS vs wild-type FLT38
    • May be a potential mechanism of treatment resistance9
  • Survival in relapsed or refractory FLT3m+ AML is especially poor1,10
    • In a retrospective, multicenter study of 138 adult patients with relapsed (n=81) or refractory (n=57) AML treated with intensive salvage chemotherapy regimens, FLT3-ITD mutations were associated with an adverse impact on OS1

NCCN Guidelines® recommend retesting all AML patients for FLT3 mutations at relapse11

Emergence of FLT3-ITD or FLT3-TKD mutations over the course of treatment Emergence of FLT3-ITD or FLT3-TKD mutations over the course of treatment

AML=acute myeloid leukemia; DFS=disease-free survival; FLT3=FMS-like tyrosine kinase 3; ITD=internal tandem duplication; m+=mutation-positive; NCCN=National Comprehensive Cancer Network; OS=overall survival; TKD=tyrosine kinase domain.