Avapritinib improves cutaneous involvement in patients with indolent systemic mastocytosis: Results from the randomized, phase 2, interventional PIONEER study

BACKGROUND: Indolent systemic mastocytosis (ISM), a clonal mast cell disease driven by the KIT D816V mutation, can often cause debilitating dermatologic symptoms. OBJECTIVE: Assess improvement of ISM-related skin manifestations after treatment with avapritinib, a highly selective KIT D816V inhibitor, vs placebo in Part 2 of the PIONEER study (NCT03731260). METHODS: Patients with moderate to severe ISM received avapritinib 25 mg once daily (n = 141) or placebo (n = 71). Endpoints included skin lesion area and pigmentation at week 24, skin mast cell burden, and change in symptoms. RESULTS: Mean percent reduction in lesional surface area was -36.6% with avapritinib vs -1.8% with placebo in the most affected area; 86% vs 0% had improved skin lesion color. Mean percent change in skin mast cell burden decreased with avapritinib (-22.1%) vs placebo (10.1%). Avapritinib vs placebo significantly improved skin symptom domain score (mean change -7.2 vs -2.8; P < .0001), including the individual skin symptoms itching, flushing, and spots. Avapritinib was well tolerated. LIMITATIONS: Photography was optional, so analysis population for lesion area and color were smaller (n = 111) than the overall study population (n = 212). CONCLUSION: Avapritinib treatment improved dermatologic symptoms, decreased skin lesion size, normalized skin lesion color, and reduced skin mast cell burden in patients with ISM.