The FDA approved midostaurin as part of combination treatment for adults with newly diagnosed FLT3–positive acute myeloid leukemia.
Midostaurin (Rydapt, Novartis) is approved for use with standard cytarabine and daunorubicin induction and cytarabine consolidation.
The FDA also approved a companion diagnostic — LeukoStrat CDx FLT3 Mutation Assay (Invivoscribe Technologies) — for use with midostaurin to test patients with AML for the FLT3 mutation.
The FDA based the approval of midostaurin on results of a randomized, double blind, placebo-controlled trial that included 717 patients with treatment-naive FLT3–positive AML.
Researchers randomly assigned patients to placebo or 50 mg oral midostaurin twice daily on days 8 to 21 of each cycle of induction and consolidation chemotherapy, followed by continuous daily midostaurin for up to 12 cycles.
Results showed midostaurin significantly improved OS (HR = 0.77; P = .016).
Adverse events that occurred in at least 20% of midostaurin-treated patients included febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia and upper respiratory tract infection.
Febrile neutropenia occurred in 16% of patients in each treatment group.
The FDA also approved midostaurin for the treatment of adults with aggressive systemic mastocytosis, those with systemic mastocytosis with an associated hematological neoplasm, and patients with mast cell leukemia.
The FDA based those approvals on results of a single-arm, open-label study of midostaurin administered in 100-mg twice-daily oral doses.
After six cycles of midostaurin, rates of confirmed complete remission plus incomplete remission by modified Valent criteria were 38% for those with aggressive systemic mastocytosis and 16% for patients who had systemic mastocytosis with associated hematological neoplasm.
One patient (5%) with mast cell leukemia achieved a complete response.
The most common adverse reactions in that trial included nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, fever, headache and dyspnea.