FDA approves new combination treatment for acute myeloid leukaemia

The US Food and Drug Administration (FDA) has approved Novartis’ Rydapt (midostaurin) for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who have a specific genetic mutation called FLT3, in combination with chemotherapy.

The drug is approved for use with a companion diagnostic, Invivoscribe Technologies’ LeukoStrat CDx FLT3 Mutation Assay, which is used to detect the FLT3 mutation in patients with AML.

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 estimated that approximately 19,930 people would be diagnosed with AML in 2016 and 10,430 were projected to die of the disease.

"Rydapt is the first targeted therapy to treat patients with AML, in combination with chemotherapy," said Richard Pazdur MD acting director of the Office of Haematology 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."

Kinase inhibitor

Rydapt 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 LeukoStrat CDx FLT3 Mutation Assay, the patient may be eligible for treatment with Rydapt in combination with chemotherapy.

Safety and efficacy

The safety and efficacy of 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 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 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 leukaemia or death) than patients who received chemotherapy alone (median three months).

Adverse reactions

Common side effects of Rydapt in patients with AML include 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. Rydapt should not be used in patients with hypersensitivity to midostaurin or other ingredients in Rydapt.

Women who are pregnant or breastfeeding should not take Rydapt because it may cause harm to a developing foetus or a newborn baby.

Patients who experience signs or symptoms of lung damage (pulmonary toxicity) should stop using Rydapt.

Rare blood disorder approval

Rydapt was also approved for adults with certain types of rare blood disorders (aggressive systemic mastocytosis, systemic mastocytosis with associated haematological neoplasm or mast cell leukaemia). Common side effects of Rydapt in these patients include nausea, vomiting, diarrhoea, swelling (oedema), 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.