Midostaurin, sold under the brand name Rydapt, is a targeted therapy medication used to treat specific types of cancer and a rare blood disorder. It belongs to a class of drugs known as kinase inhibitors, which are designed to interfere with signaling pathways that control cell growth and division.
What Midostaurin Treats
Midostaurin is approved for the treatment of newly diagnosed Acute Myeloid Leukemia (AML) in adults. Its use is specific to patients whose cancer cells have a genetic feature known as an FLT3 mutation. This mutation is present in about 30% of AML cases and contributes to the rapid growth of leukemia cells.
The medication is also used to treat a group of rare blood disorders known as advanced Systemic Mastocytosis (SM). This condition is characterized by the excessive accumulation of mast cells in various tissues and organs. Midostaurin is indicated for adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).
Mechanism of Action
Midostaurin functions by blocking the activity of proteins called kinases. Kinases act as molecular switches inside cells, sending signals that tell the cell when to grow and divide. In many forms of cancer, these kinase switches become defective and get stuck in the “on” position, leading to uncontrolled cell division.
Midostaurin is a multi-targeted kinase inhibitor, meaning it blocks several of these overactive switches. Its effectiveness in treating Acute Myeloid Leukemia (AML) comes from its inhibition of a kinase called FLT3. In patients with an FLT3 mutation, this receptor sends continuous growth signals to leukemia cells. Midostaurin blocks the FLT3 receptor, shutting down this pathway and inducing programmed cell death in the cancerous cells.
A similar mechanism applies to its treatment of advanced Systemic Mastocytosis. In this disease, the abnormal proliferation of mast cells is often driven by mutations in a different kinase called KIT. Midostaurin also inhibits the KIT kinase. By blocking KIT signaling, the drug helps reduce the number of mast cells, control their proliferation, and interfere with the release of substances like histamine that contribute to symptoms.
Administration and Patient Monitoring
Midostaurin is an oral medication in the form of a soft capsule, taken twice a day about 12 hours apart. Patients should take the capsules with food, as this increases the body’s absorption of the drug and can help reduce nausea.
For patients with AML, the dosing schedule is integrated with their chemotherapy. The medication is taken for a 14-day period, from day 8 to day 21 of each 28-day induction and consolidation chemotherapy cycle. In the treatment of advanced systemic mastocytosis, it is taken continuously every day until the disease progresses or unacceptable toxicity occurs.
Due to the medication’s effects, regular patient monitoring is necessary. This involves frequent blood tests to check blood cell counts, including neutrophils, red blood cells, and platelets, as the drug can cause bone marrow suppression. Physicians also monitor liver and kidney function through blood work to detect any potential organ toxicity early.
Potential Side Effects
Patients taking midostaurin may experience a range of side effects. The most common effects include:
- Febrile neutropenia (a low white blood cell count accompanied by a fever)
- Nausea, vomiting, and diarrhea
- Mucositis (painful inflammation and sores in the mouth)
- Headaches
- Musculoskeletal pain
- Fatigue
Some side effects are more serious and require immediate medical attention. The suppression of the immune system can lead to severe infections. Patients may also develop high blood sugar (hyperglycemia). While nausea and vomiting are common, they can become severe, potentially requiring a temporary pause in treatment or a dose adjustment.
Important Safety Considerations
Midostaurin can interact with many other drugs, which can alter its effectiveness and increase the risk of side effects. It is metabolized in the liver by an enzyme known as CYP3A4. Medications that are strong inhibitors of CYP3A4 can increase midostaurin concentrations in the blood, while strong inducers can lower its concentration, making it less effective. Patients must inform their healthcare provider about all medications they use, including prescription, over-the-counter, and herbal supplements.
A specific warning for midostaurin is the risk of serious lung problems, such as interstitial lung disease and pneumonitis. Patients are advised to report any new or worsening respiratory symptoms, like coughing or shortness of breath, to their doctor immediately.
The medication can cause harm to a developing fetus and should not be taken during pregnancy. Women of reproductive potential must have a negative pregnancy test before starting therapy and use effective contraception during treatment and for at least four months after the final dose. Men receiving midostaurin should also use effective contraception.