Avapritinib Shows Dermatologic Benefits in Indolent Systemic Mastocytosis

Key Takeaways

• Avapritinib significantly improved skin lesion size, pigmentation, mast cell burden, and patient-reported skin symptoms in adults with indolent systemic mastocytosis (ISM).
• In the phase 2 PIONEER trial, 86% of avapritinib-treated patients experienced improved skin lesion color compared with 0% of placebo-treated patients.
• Improvements in itching, flushing, and skin spots were observed as early as 4 weeks.

Treatment with avapritinib led to substantial improvements in cutaneous disease manifestations among patients with indolent systemic mastocytosis (ISM), according to results from the phase 2 PIONEER study.

Investigators for the second part of the PIONEER trial evaluated 212 adults with moderate-to-severe ISM who received either avapritinib 25 mg daily plus best supportive care (n = 141) or placebo plus best supportive care (n = 71) for 24 weeks.

PIONEER Trial Shows Improvements in Skin Lesions, Symptoms, and Mast Cell Burden

Among patients with available skin photography, avapritinib produced a mean 36.6% reduction in lesion surface area in the most affected region compared with a 1.8% reduction with placebo. Skin lesion color improvement was also reported: 86% of avapritinib-treated patients experienced normalization or improvement vs none with placebo.

Biopsy analyses showed eductions in skin mast cell burden with avapritinib (mean decrease, 22.1% vs 10.1% placebo). Investigators also reported improvements in patient-reported skin symptoms such as itching, flushing, and skin spots. Mean skin-domain symptom scores improved by 7.2 points with avapritinib vs 2.8 points with placebo (P < 0.0001). The study's primary limitation was that skin photography was optional, resulting in a smaller analysis population for lesion area and pigmentation assessments. Authors noted that avapritinib was generally well tolerated with an acceptable safety profile.

“Avapritinib treatment improved dermatologic symptoms, decreased skin lesion size, normalized skin lesion color, and reduced skin mast cell burden in patients with ISM,” the authors concluded.

Source

Siebenhaar F, et al. JAAD. 2026. Doi:10.1016/j.jaad.2026.02.025