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
  • In a study, 3 independent factors were identified to have a highly negative impact on prognosis in AML1:
    • Disease status: refractory and early relapse between 6 and 12 months
    • FLT3 mutation
    • High-risk cytogenetics
Mutations in FLT3 are the most common mutations in AML3
  • These mutations typically result in either an internal tandem duplication (ITD) of amino acids in the juxtamembrane region of the FLT3 protein or, less frequently, a point mutation in the activation loop of the tyrosine kinase domain (TKD)4
    • Both ITD and TKD mutations result in constitutive activation of the FLT3 kinase
FLT3-ITD mutation positive3

For patients with AML who have relapsed and are positive for FLT3-ITD mutations, the prognosis is significantly poorer than for other patients with AML1,2

  • FLT3-ITD mutations are associated with negative prognosis in patients with AML compared to patients with wild-type FLT3, including5,6:
    • Higher risk of relapse5,6
    • Increased risk of death6
  • FLT3-ITD mutations are one of the significant, independent prognostic factors for negative patient outcomes after first relapse1,2
FLT3-TKD mutation positive3

The impact of FLT3-TKD mutations on prognosis is less clear4

  • In some studies, FLT3-TKD mutations showed no prognostic significance4
  • One study demonstrated that prognosis may depend on other genetic aberrations7

FLT3-TKD mutations may be a potential mechanism of treatment resistance8

  • In some patients with FLT3-ITD mutations alone prior to treatment with a FLT3 inhibitor, FLT3-TKD mutations may emerge at the end of therapy

For patients with relapsed or refractory FLT3m+ AML, there have been no FDA-approved targeted treatments.9
Until Now.

AML=acute myeloid leukemia; FDA=Food and Drug Administration; FLT3=FMS-like tyrosine kinase 3; ITD=internal tandem duplication; m+=mutation-positive; TKD=tyrosine kinase domain.