A PIONEER trial has been conducted in order to evaluate the effects of avapritinib, a drug meant to treat systematic mastocytosis. Researchers want to find a better treatment for this disease as many people who receive the already available therapy still experience symptoms. This is why they are excited about the results of phase II of their clinical trial, as none of the participants experienced adverse effects or discontinued their treatment. Researchers are hopeful that results will continue to be positive as they conduct more research.
About Systematic Mastocytosis
Systematic mastocytosis is characterized by the accumulation of of mast cells in internal tissue, such as the liver, spleen, bone marrow, and small intestines. There are four types of this disease, which are indolent systematic mastocytosis (ISM), systematic mastocytosis with an associated hematologic nonmast cell lineage disorder (SM-AHNMD), aggressive systematic mastocytosis (ASM), and mast cell leukemia (MCL). It is important that the type is found, as it can greatly affect the treatment method that doctors select.
This disease is caused by a mutation in the KIT gene, which is responsible for making receptor tyrosine kinases. If there is a change in the function of this protein, there can be problems with cell division, growth, survival, and movement. In this case, mast cells are affected, and they accumulate in the internal tissue. While most cases are sporadic, some familial cases have been reported. In these cases, the inheritance of the gene is an autosomal dominant pattern.
Symptoms of this disease depend on the type and location of accumulation, but there are common symptoms to all four forms. These include anemia and bleeding disorders, abdominal pain, diarrhea, nausea, vomiting, itching hives, flushing of the skin, anaphylactoid reactions, and enlargement of the spleen, liver, or lymph nodes. In terms of the types of systematic mastocytosis, ISM is the least severe type and sees the slowest progression. SM-AHNMD is associated with other blood disorders, so symptoms can come from those conditions as well. ASM is a severe form and usually comes with organ failure. MCL is very rare and very aggressive.
After doctors ensure that it is systematic mastocytosis, they will determine treatment based on the type, severity, and symptoms of the patient. Treatment is symptomatic and includes antihistamines for skin and gastrointestinal symptoms, proton pumps for increased stomach acid, epinephrine for anaphylaxis, steroids to aid in the absorption of nutrients, mast cell stabilizers for skin symptoms, and cromolyn sodium for headaches, bone pain, gastrointestinal, and skin symptoms. If one has MCL then chemotherapy may be necessary. SM-AHNMD may also require different treatments due to its association with other blood disorders.
About the Study
Blueprint Medicines Corporation, which is a precision therapy company, has conducted the PIONEER clinical trial in an effort to evaluate avapritinib. They recently performed the second phase of this trial, after the first phase found that avapritinib reduced serum tryptase, which is a measure of mast cell burden. The first phase also found that different doses, 25 mg, 50 mg and 100 mg, were all successful in this reduction and did not produce significant adverse effects. The next phase of the trial will test long term treatment, and all of the 112 participants who completed the first two phases are eligible. This treatment inhibits the mutated form of the KIT gene. Blueprint Medicines plans to send an application of avapritinib for the treatment of systematic mastocytosis to the FDA in the first quarter of 2020.
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