Avapritinib reduces symptoms and mast cell burden in systemic mastocytosis.

Background: Mastocytosis is driven by a clonal expansion of mast cells, commonly triggered by the KIT D816V mutation which is present in over 90% of adult patients. Individuals with indolent systemic mastocytosis (ISM) frequently experience recurrent anaphylaxis and mast cell mediator-related symptoms, leading to substantial morbidity. In rare cases, progression to more severe subtypes, such as smoldering systemic mastocytosis (SSM), can occur.

Case presentation: We describe one patient with ISM and another with ISM transitioning to SSM, both treated with the selective KIT D816V inhibitor avapritinib at a daily dose of 25 mg. Following initiation of avapritinib, both patients exhibited a marked reduction in serum tryptase levels and complete remission of maculopapular cutaneous mastocytosis. Additionally, joint pain, gastrointestinal symptoms, and neurocognitive complaints decreased. Sustained clinical improvement over follow-up periods of 9 and 12 months was consistently reflected in disease-specific patient-reported outcome measures (PROMs).

Conclusions: Regular clinical and laboratory monitoring, including serum tryptase and KIT D816V mutation assessment in peripheral blood, is essential in all ISM patients to detect early signs of disease progression. In refractory cases, avapritinib is a promising therapeutic option that can reduce mast cell burden, alleviate symptoms, and enhance overall quality of life.