In patients with indolent systemic mastocytosis (ISM), treatment with avapritinib reduced disease-related symptoms and improved quality of life at four years, according to updated findings from the PIONEER clinical trial (NCT03731260).
The results, which were recently presented at the European Academy of Allergy & Clinical Immunology 2026 annual meeting in Istanbul, support the continued use of avapritinib as a safe and effective option for individuals with ISM.
Avapritinib targets and inhibits the KIT D816V protein, which is responsible for about 95% of ISM cases. The drug is currently approved in the United States for adults with ISM (as well as advanced subtypes of SM) and in the European Union for those with moderate to severe ISM (and, as in the U.S., advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm.).
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The study included 226 participants from parts 1 and 2 of the PIONEER study who opted into the open-label extension, for a median treatment duration of four years. Individuals received 25 mg avapritinib daily, with some receiving 50 mg per investigator discretion.
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The researchers measured symptom burden via the ISM-Symptom Assessment Form, which analyzed self-reported disease severity on a 110-point scale. At four years, participants reported an average reduction in symptom burden of 17.66 points.
Moreover, quality of life, measured via the 100-point MastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. Quality of Life Questionnaire, improved by a mean of 35.41 percentage points at four years. Just over half of participants reported that SM limited their ability to work or attend school less often. Likewise, 58.2% reported a reduced impact of SM on their interpersonal relationships.
The study also evaluated changes in best supportive care (BSC) medications, finding that 52% of participants reduced or discontinued at least one BSC class at three years. BSC classes with the largest reductions in use included cromolyn sodium, anti-immunoglobulin E treatment and both H1 and H2 antihistaminesAntihistamines Medications that block the effects of histamine, the chemical found in mast cells that is responsible for many of the symptoms of SM, as well as many allergic reactions..
“Overall, these 4-year data demonstrate that avapritinib can simultaneously achieve durable reductions in disease-related symptoms, long-term improvements in [quality of life], and decrease the amount of BSC medications used, all while maintaining a well-tolerated and well-characterized safety profile,” the authors concluded.
