Avapritinib for the Treatment of Indolent Systemic Mastocytosis

Abstract

Indolent systemic mastocytosis (ISM) is a disorder characterized by an accumulation of mast cells in subdermal tissue that leads to exaggerated immune response after release of mast cells mediators. Routinely administered treatments include H1 and H2 receptor antagonists, mast cell stabilizers, corticosteroids, and more recently anti-IgE antibody therapies. Our case presentation explores the treatment of indolent mastocytosis with avapritinib, an antineoplastic, after routine treatment options failed.A 64-year-old female with history of obesity presented to a community-based Allergy/Immunology clinic with chief complaints of recurrent throat tightness, fatigue, headaches, brain fog. She was found to have high tryptase levels which remained persistently elevated from 46 to 55 (include units) over 13-month span. Physical exam was grossly unremarkable.Bone marrow biopsy showed mast cell aggregates highly suspicious for ISM. PCR for KIT (D816V) mutation was positive. Initial treatment included fexofenadine 180 mg and famotidine 20 mg both twice daily. Overall, she had less frequent episode of throat tightness over 9 months, but itchiness, fatigue, brain fog persisted. Monthlyomalizumab 300 mg was added on but was eventually discontinued to lack of benefit. She was referred to a tertiary center where avapritinib 25 mg daily was started. Four months after initiation, occurrences of throat tightness, stomach cramps, and vomiting resolved, and came off all other therapies for mastocytosis. Eight months after avapritinib initiation tryptase had decreased to 19.Avapritinib is a selective kinase inhibitor used to avoid resistance in patients undergoing chemotherapy with indications in those with advanced systemic mastocytosis and neoplastic complications. The mechanism of action of avapritinib includes inhibition of KIT and PDGFRA mutations. Treatment in our patient resulted in the successful symptomatic treatment of indolent systemic mastocytosis targeting KIT (D816V). This case demonstrates a new treatment which may improve the quality of life of individuals with ISM.