FDA Approves Midostaurin Combination for AML and Systemic Mastocytosis

The U.S. Food and Drug Administration (FDA) approved midostaurin in combination with 7+3 induction and consolidation chemotherapy with daunorubicin and cytarabine for the treatment of adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML), and as monotherapy for patients with aggressive systemic mastocytosis (SM) or SM with associated hematologic neoplasm or mast cell leukemia. Midostaurin was approved for use with a companion diagnostic tool, the LeukoStrat CDx FLT3 Mutation Assay, which is used to detect the FLT3 mutation in patients with AML.

Midostaurin is an oral, multitarget protein kinase inhibitor and the first FDA-approved targeted therapy to treat patients with AML. The approval was based on results from the randomized RATIFY trial, which evaluated the safety and efficacy of midostaurin in 717 patients who had not been treated previously for their FLT3-mutated AML. In the trial, patients who received midostaurin and chemotherapy had longer survival than those who received chemotherapy alone; however, a specific median survival rate could not be reliably estimated. Midostaurin-treated patients also continued on the trial longer without certain complications (including failure to achieve complete remission within 60 days of starting treatment, progression of leukemia, or death) than patients who received chemotherapy alone (median duration = 8.2 vs. 3 months).

The most common adverse events (AEs) included febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, and upper respiratory tract infection. The FDA approval notes that midostaurin should not be used in women who are pregnant or breastfeeding, and patients who show signs or symptoms of pulmonary toxicity should stop using midostaurin.

Midostaurin was previously granted priority review, as well as fast-track and breakthrough-therapy designations.

Source: U.S. Food and Drug Administration news release, April 28, 2017.