FDA Approves Midostaurin in Combination With Chemotherapy for Newly Diagnosed FLT3-Positive Acute Myeloid Leukemia


On April 28, 2017, the U.S. Food and Drug Administration (FDA) approved midostaurin (Rydapt) for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation–positive, as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation.

The FDA also approved a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay, for use with midostaurin to test patients with AML for the FLT3 mutation.


Approval was based on the randomized, double-blind, placebo-controlled RATIFY trial in 717 patients with previously untreated FLT3 mutation–positive AML. This trial randomized patients to either placebo or midostaurin at 50 mg orally 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. The trial demonstrated a statistically significant improvement in overall survival for patients receiving midostaurin compared with those on the placebo-containing arm (hazard ratio = 0.77, P = .016).

Common adverse reactions, occurring in at least 20% of patients, included febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, and upper respiratory tract infection. The most frequent serious adverse reaction was febrile neutropenia, occurring in 16% of patients on both arms.

Mast Cell Leukemia

The FDA also approved midostaurin for the treatment of adults with aggressive systemic mastocytosis (with or without associated hematologic neoplasm) or mast cell leukemia. Approval was based on response rate and duration in a single-arm, open-label study of midostaurin at 100 mg orally twice daily.

With 6 cycles of midostaurin, the rates of confirmed complete remission plus incomplete remission by modified Valent criteria were 38% for aggressive systemic mastocytosis and 16% for systemic mastocytosis with associated hematologic neoplasm. One patient (5%) with mast cell leukemia achieved a complete remission. The most common adverse reactions 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 systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm, or mast cell leukemia is 100 mg twice daily with food.

Full prescribing information is available at:

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.