Avapritinib Durably Improves Cutaneous Involvement of Indolent Systemic Mastocytosis in Patients Treated in the PIONEER Study

Abstract

Introduction: Indolent systemic mastocytosis (ISM) is a clonal mast cell (MC) disease primarily driven by D816V-mutant KIT. ISM is characterized by accumulation and hyperactivation of aberrant MCs in organs including skin, often leading to skin-related symptoms. Skin findings were characterized in patients with ISM treated with avapritinib, a potent, selective KIT D816V inhibitor, in PIONEER (NCT03731260).

Methods: Long-term safety and efficacy of avapritinib 25 mg once daily plus best supportive care was evaluated in 226 patients with ISM. Skin symptoms were evaluated by the ISM-Symptom Assessment Form skin domain score (0–30) and individual skin symptoms (0–10) of spots, itching, and flushing from baseline to 48 and 144 weeks. Changes in skin lesions by photography were captured until 48 weeks.

Results: Mean (standard deviation [SD]) change from baseline in the skin symptom domain was −6.89 (7.11) at Week 48 and −2.48 (2.50), –2.45 (2.82), –1.95 (2.72) for spot severity, itching, and flushing, respectively. At Week 144, the mean (SD) change in skin symptom domain was –8.14 (7.86). Patients with paired photographs (n=51) showed a median percent reduction in lesion surface area in the most affected skin region of –60% after 48 weeks; 82% had lightened skin lesion color. Long-term follow-up (up to 5 years; median 3 years) demonstrated avapritinib was generally well tolerated with no new safety concerns observed.

Conclusion: Avapritinib provided sustained and durable improvements in skin manifestations of ISM and demonstrated a favorable benefit–risk profile, highlighting the ability of avapritinib to achieve long-term disease modification.