LeukoStrat CDx FLT3 Mutation Assay: New entry in the field of companion tests

AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of white blood cells in the bloodstream. The National Cancer Institute (NCI) estimated that in the US, approximately 19,930 people would be diagnosed with AML in 2016 and 10,430 were projected to die of the disease.

According to Richard Pazdur, the 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, Midostaurin (Rydapt) is the first targeted therapy to treat patients with AML, in combination with chemotherapy, and the ability to detect the particular gene mutations with a diagnostic test means doctors can identify specific patients who may benefit from this treatment. Midostaurin (Rydapt) is a kinase inhibitor that works by blocking several enzymes that promote cell growth. If the particular FLT3 mutations are detected in blood or bone marrow samples using the LeukoStrat CDx FLT3 Mutation Assay, the patient may be eligible for treatment with Midostaurin (Rydapt) in combination with chemotherapy.

The safety and efficacy of Midostaurin (Rydapt) 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 (Rydapt) 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 (Rydapt) 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 three months).

In contrast, common side effects of Midostaurin (Rydapt) in this set of patients with AML included low levels of white blood cells with fever (febrile neutropenia), nausea, inflammation of the mucous membranes (mucositis), vomiting, headache, spots on the skin due to bleeding (petechiae), musculoskeletal pain, nosebleeds (epistaxis), device-related infection, high blood sugar (hyperglycemia) and upper respiratory tract infection. Midostaurin (Rydapt) should not be used in patients with hypersensitivity to midostaurin or other ingredients in Midostaurin (Rydapt). Women who are pregnant or breastfeeding should not take Midostaurin (Rydapt) because it may cause harm to a developing fetus or a newborn baby. Patients who experience signs or symptoms of lung damage (pulmonary toxicity) should stop using Midostaurin (Rydapt).

Midostaurin (Rydapt) was also approved today for adults with certain types of rare blood disorders (aggressive systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm or mast cell leukemia). Common side effects of Midostaurin (Rydapt) in these patients include nausea, vomiting, diarrhea, swelling (edema), musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, constipation, fever, headache and shortness of breath.

The FDA granted this application Priority Review, Fast Track (for the mastocytosis indication) and Breakthrough Therapy (for the AML indication) designations.