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

## TL;DR

This study examines anaphylaxis events in patients with indolent systemic mastocytosis treated with avapritinib, a KIT D816V inhibitor.

## Contribution

The study reports the incidence of anaphylaxis in ISM patients during avapritinib treatment and compares it to placebo.

## Key findings

- 6.1% of patients in the PIONEER study experienced anaphylaxis during screening or treatment.
- Avapritinib-treated patients had a lower rate of anaphylaxis compared to placebo-treated patients during the treatment period.

## Abstract

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.

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.

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.

Larger studies with longer-term follow-up are required to further confirm the effects of avapritinib on anaphylaxis in patients with SM.