The Food and Drug Administration has approved midostaurin for the treatment of FLT3 mutation–positive acute myeloid leukemia (FLT3+ AML) in adult patients in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation.
Approval was based on results from a randomized, double-blind, placebo-controlled trial of 717 patients with previously untreated FLT3+ AML. The hazard ratio for overall survival in patients receiving midostaurin, compared with a placebo, was 0.77 (P = .016). A companion diagnostic tool, the LeukoStrat CDx FLT3 Mutation Assay manufactured by Invivoscribe Technologies, was also approved.
Midostaurin was also approved for the treatment of aggressive systemic mastocytosis, SM with associated hematological neoplasm, or mast cell leukemia. This indication approval was based on a single-arm, open-label study of midostaurin 100 mg, taken orally twice daily. Complete plus incomplete remission rates were 38% for ASM and 16% for SM with associated hematological neoplasm. Common adverse events included nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, fever, headache, and dyspnea.
The recommended dose of midostaurin in AML is 50 mg twice daily with food on days 8 to 21 of each cycle of induction and consolidation chemotherapy followed by 50 mg with food as a single agent for up to 12 months. The recommended dose for the treatment of adults with aggressive SM, SM with associated hematological neoplasm, or mast cell leukemia is 100 mg twice daily with food, the FDA said.
Midostaurin will be marketed as Rydapt by Novartis Pharmaceuticals.