The FDA recently approved midostaurin in combination with chemotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who have the FLT3 genetic mutation. The drug is approved for use with a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay, which is used to detect the FLT3 mutation in patients with AML.
"Midostaurin is the first targeted therapy to treat patients with AML, in combination with chemotherapy," said Richard Pazdur, MD, Acting Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, and Director of the FDA's Oncology Center of Excellence. "The ability to detect the gene mutation with a diagnostic test means doctors can identify specific patients who may benefit from this treatment."
Midostaurin is a kinase inhibitor that works by blocking several enzymes that promote cell growth. If the FLT3 mutation is detected in blood or bone marrow samples using the companion diagnostic assay, the patient may be eligible for treatment with midostaurin in combination with chemotherapy.
The safety and efficacy of midostaurin for patients with AML were studied in a randomized trial of 717 patients who had not been treated previously for AML. In the trial, patients who received midostaurin in combination with chemotherapy lived longer than patients who received chemotherapy alone, although a specific median survival rate could not be reliably estimated. In addition, patients who received midostaurin in combination with chemotherapy in the trial went longer (median 8.2 months) without certain complications (failure to achieve complete remission within 60 days of starting treatment, progression of leukemia, or death) than patients who received chemotherapy alone (median 3 months).
Common side effects include febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, and upper respiratory tract infection. Midostaurin should not be used in patients with hypersensitivity to midostaurin or other ingredients in the drug. Women who are pregnant or breastfeeding should not take midostaurin because it may cause harm to a developing fetus or a newborn baby. Patients who experience signs or symptoms of pulmonary toxicity should stop using midostaurin.
The drug was also approved for adults with certain types of rare blood disorders, including aggressive systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm, or mast cell leukemia.
The FDA granted this application Priority Review, Fast Track (for the mastocytosis indication), and Breakthrough Therapy (for the AML indication) designations.