The first targeted drug with FDA approval for acute myeloid leukemia: Midostaurin

On April 28, 2017, the FDA approved midostaurin (brand name Rydapt) for newly diagnosed adult acute myeloid leukemia (AML) with FLT3 mutation positivity (FLT3 +), detected by an FDA-approved test.

Approval was based on a comprehensive study of previously untreated FLT3 + AML involving 717 patients. They received standard induction with cytarabine plus daunorubicin and consolidation with cytarabine, on chemotherapy cycle days 8-21, then up to 12 cycles, with daily oral placebo or 50 mg midostaurin twice daily in 2 arms. Overall survival was longer with midostaurin than placebo (an intervention without active ingredient): %23 longer than standard treatment.

Midostaurin mechanism of action

Midostaurin is a multikinase inhibitor and the first targeted agent approved for acute myeloid leukemia treatment. Kinases are proteins on the cytoplasmic side of the cell membrane mediating signals promoting cell proliferation.

Possible side effects

Common side effects occurring in at least % 20 include low white blood cells with fever (neutropenia), nausea, mouth sores (mucositis), vomiting, headache, skin rash (petechiae), musculoskeletal pain, nosebleeds, device-related infection, high blood sugar (hyperglycemia) and upper respiratory infection. The most common serious side effect was low white blood cells with fever, occurring in % 16 of both placebo and midostaurin patients.

The American Food and Drug Administration FDA also approved midostaurin for adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematologic neoplasm (SM-AHN) or mast cell leukemia.

Administration and dosage

The recommended AML dose is twice-daily midostaurin with food at 50 mg on induction and consolidation chemotherapy days 8-21, then daily as a single agent for up to 12 months. For adults with aggressive systemic mastocytosis, SM associated with hematologic neoplasm or mast cell leukemia, the recommended dose is twice daily with food at 100 mg.

The FDA also approved, for detecting FLT3 mutations in AML patients using midostaurin, the LeukoStrat CDx FLT3 Mutation Test.