Avapritinib improves cutaneous involvement in patients with indolent systemic mastocytosis: Results from the randomized, phase 2, interventional PIONEER study
Year: 2026
Type: article
Abstract: 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.
Authors: Frank Siebenhaar, Sigurd Broesby-Olsen, Mariana Castells, Tracy I. George, Cristina Bulai Livideanu, Iván Álvarez-Twose, Jens Panse, Stéphane Barete, Andreas Reiter, Ingunn Dybedal, Cem Akin, Paul Van Daele, Deepti H. Radia, Sonia Cerquozzi, Celalettin Ustun, Vito Sabato, Jason Gotlib, Mark Rafferty, Daniel J. DeAngelo, Philippe Schafhausen, Johanna Ungerstedt, Princess U. Ogbogu, Scott Florell, David A. Wada, Anton Rets, Hui-Min Lin, Ilda Bidollari, Janet Hong, Daniel Shaheen, Benjamin Lampson, Karin Hartmann
Institutions: Humboldt-Universität zu Berlin, Fraunhofer Institute for Translational Medicine and Pharmacology, Freie Universität Berlin, Charité - Universitätsmedizin Berlin, Odense University Hospital, Brigham and Women's Hospital, Harvard University, University of Utah, Huntsman Cancer Institute, ARUP Laboratories (United States), Centre Hospitalier Universitaire de Toulouse, Hôpital Larrey, Hospital Virgen del Valle, Universitätsklinikum Aachen, RWTH Aachen University, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Heidelberg University, University Medical Centre Mannheim, Oslo University Hospital, University of Michigan, Erasmus MC, Guy's and St Thomas' NHS Foundation Trust, University of Calgary, Rush University Medical Center, Rush University, University of Antwerp, Antwerp University Hospital, Stanford Cancer Institute, Stanford University, Beatson West of Scotland Cancer Centre, Dana-Farber Cancer Institute, University Medical Center Hamburg-Eppendorf, Karolinska Institutet, Rainbow Babies & Children's Hospital, Case Western Reserve University, Blueprint Medicines (United States), University of Basel, University Hospital of Basel
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
OpenAlex ID: W7128705245