J Am Acad Dermatol

Targeted therapy significantly reduces skin lesions in indolent systemic mastocytosis

March 23, 2026

Part 2 of the PIONEER trial evaluated avapritinib 25 mg daily vs. placebo in 212 patients with moderate‑to‑severe indolent systemic mastocytosis (ISM). At 24 weeks, avapritinib led to a mean 36.6% reduction in lesional surface area compared with 1.8% with placebo, and 86% vs. 0% of patients showed improved lesion color. Skin mast‑cell burden decreased by 22.1% with avapritinib but increased by 10.1% with placebo. Participants also reported greater relief in itching, flushing, and skin spots, reflected in a significantly larger improvement in the skin symptom domain score (–7.2 vs. –2.8; p<.0001). Avapritinib was well tolerated. Photography‑based endpoints had smaller sample sizes because imaging was optional.

Clinical takeaway: For patients with indolent systemic mastocytosis and persistent, bothersome cutaneous symptoms despite standard therapy, avapritinib may offer an effective targeted option to improve skin involvement and overall symptom control.

Source:

Siebenhaar F, et al. (2026, February 12). J Am Acad Dermatol. Avapritinib improves cutaneous involvement in patients with indolent systemic mastocytosis: Results from the randomized, phase 2, interventional PIONEER study. https://pubmed.ncbi.nlm.nih.gov/41690487/