Anaphylaxis events in the PIONEER study of avapritinib in indolent systemic mastocytosis

Background: Patients with indolent systemic mastocytosis (ISM), a clonal mast cell disease primarily driven by the KIT D816V mutation, often have lifelong debilitating symptoms.Anaphylaxis is a common feature of the disease seen in up to half of patients.The effects of KIT D816V-targeted therapy on the incidence of anaphylaxis are unknown. Methods:We describe anaphylaxis events occurring in the study population of PIONEER (NCT03731260) during the 12-week screening and/or 24-week treatment period.This study had previously demonstrated the efficacy and safety of the oral, highly selective, KIT D816V inhibitor avapritinib compared with placebo in patients with moderate-to-severe ISM. Results:In total, 13/212 (6.1%) patients in PIONEER experienced anaphylaxis during screening or treatment (6 during screening, 5 during treatment, and 2 during both screening and treatment).Baseline demographics, clinical characteristics, and known triggers varied.During the randomized, placebo-controlled treatment period, 4/141 (2.8%) avapritinib-treated patients and 3/71 (4.2%) placebo-treated patients experienced anaphylaxis. Conclusions:Larger studies with longer-term follow-up are required to further confirm the effects of avapritinib on anaphylaxis in patients with SM.