PIONEER Skin Assessments Supplemental Material

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.

These data are the supplemental material for the primary publication of PIONEER Skin Assessments in JAAD.

背景：
惰性系统性肥大细胞增多症（Indolent Systemic Mastocytosis, ISM）是一种由KIT D816V突变驱动的克隆性肥大细胞疾病，常可引发衰弱性皮肤症状。

研究目的：
在PIONEER研究第二部分（NCT03731260）中，评估高选择性KIT D816V抑制剂阿伐普利尼（avapritinib）对比安慰剂对ISM相关皮肤表现的改善效果。

方法：
中度至重度惰性系统性肥大细胞增多症患者接受阿伐普利尼25mg每日一次治疗（n=141）或安慰剂治疗（n=71）。研究终点包括第24周时的皮损面积与色素沉着情况、皮肤肥大细胞负荷量，以及症状变化幅度。

结果：
最受累区域的皮损表面积平均减少率：阿伐普利尼组为-36.6%，安慰剂组为-1.8%；皮损颜色改善的患者占比分别为86%与0%。皮肤肥大细胞负荷量的平均变化率：阿伐普利尼组为-22.1%，安慰剂组为10.1%。阿伐普利尼较安慰剂可显著改善皮肤症状领域评分（平均变化值分别为-7.2与-2.8；p<.0001），涵盖瘙痒、潮红与斑点等单项皮肤症状。阿伐普利尼的耐受性良好。

局限性：
摄影为可选操作，因此皮损面积与颜色分析的研究人群（n=111）小于整体研究人群（n=212）。

结论：
阿伐普利尼治疗可改善惰性系统性肥大细胞增多症患者的皮肤症状、缩小皮损体积、恢复皮损颜色正常化，并降低皮肤肥大细胞负荷。

本数据为发表于《美国皮肤病学会杂志（Journal of the American Academy of Dermatology, JAAD）》的PIONEER皮肤评估研究主要论文的补充材料。