Title: Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

Stone, RM et al.


What You Need to Know:

In patients with newly diagnosed acute myeloid leukemia (AML) and a FLT3 mutation, addition of the multitargeted kinase inhibitor, midostaurin, to standard chemotherapy prolonged both overall survival as well as event-free survival.

Trial Design:

  • Phase 3 trial evaluated the effect of the addition of midostaurin to standard chemotherapy had on overall survival in 18 to 59-year old patients with newly diagnosed AML and a FLT3 mutation
  • 717 patients were randomized to receive standard chemotherapy + midostaurin (n=360) or standard chemotherapy + placebo (n=357)
  • Standard chemotherapy: included induction therapy (daunorubicin + cytarabine) and consolidation therapy (high-dose cytarabine)
  • Maintenance therapy with midostaurin or placebo was administered to patients who were in remission following consolidation therapy
  • “Randomization was stratified according to subtype of FLT3 mutation: point mutation in the tyrosine kinase domain (TKD) or internal tandem duplication (ITD) mutation with either a high ratio (>0.7) or a low ratio (0.05 to 0.7) of mutant to wild-type alleles (ITD [high] and ITD [low], respectively)”
  • Primary endpoint: overall survival

Key Outcomes:

  • FLT3 subtype: ITD (high) (n=214); ITD (low) (n=341); TKD (n=162)
  • Baseline demographics were similar among treatment groups, however 51.7% of the midostaurin group were women compared to 59.4% of the placebo group (P=0.04)
  • Overall survival: significantly longer in patients who received midostaurin vs those who received placebo (HR for death: 0.78; P=0.009
  • Event-free survival: significantly longer in midostaurin patients vs placebo patients (HR for event or death: 0.78; P=0.002, respectively)
  • “The benefit of midostaurin was consistent across all FLT3 subtypes”
  • Similar rates of severe adverse events were observed for both treatment groups