Avapritinib improves cutaneous involvement in patients with indolent systemic mastocytosis: Results from the randomized, phase 2, interventional PIONEER study - 19/05/26

Doi : 10.1016/j.jaad.2026.02.025

Frank Siebenhaar, MD ^a,^b, Sigurd Broesby-Olsen, MD ^c, Mariana Castells, MD, PhD ^d, Tracy I. George, MD ^e, Cristina Bulai Livideanu, MD, PhD ^f, Iván Álvarez-Twose, MD, PhD ^g, Jens Panse, MD ^h,ⁱ, Stéphane Barete, MD, PhD ^j, Andreas Reiter, MD ^k, Ingunn Dybedal, MD, PhD ^l, Cem Akin, MD, PhD ^m, Paul Van Daele, MD, PhD ⁿ, Deepti H. Radia, MD ^o, Sonia Cerquozzi, MD ^p, Celalettin Ustun, MD ^q, Vito Sabato, MD, PhD ^r, Jason Gotlib, MD, MS ^s, Mark Rafferty, MBChB, BSC(Med Sci), MRCP(UK) ^t, Daniel J. DeAngelo, MD, PhD ^u, Philippe Schafhausen, MD ^v, Johanna Ungerstedt, MD, PhD ^w, Princess U. Ogbogu, MD ^x, Scott Florell, MD ^y, David A. Wada, MD ^y, Anton Rets, MD, PhD ^e, Hui-Min Lin, PhD ^z, Ilda Bidollari, MD, MBA ^z, Janet Hong, PharmD ^z, Daniel Shaheen, PharmD ^z, Benjamin Lampson, MD, PhD ^z, Karin Hartmann, MD ^aa,^ab,^ac,^⁎

^a Institute of Allergology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

^b Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany

^c Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark

^d Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

^e ARUP Laboratories and Huntsman Cancer Institute, Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah

^f Department de dermatologie, Expert Centre of Mastocytosis (CEREMAST) CHU de Toulouse, Toulouse University Hospital - Larrey Hospital, Toulouse, France

^g Institute of Mastocytosis Studies of Castilla-La Mancha, Virgen del Valle Hospital, Toledo, Spain

^h Department of Oncology, Hematology, Hemostaseology, and Stem Cell Transplantation, University Hospital Aachen, Medical Faculty, RWTH Aachen University, Aachen, Germany

ⁱ Center for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf (ABCD), Aachen, Germany

^j Unit of Dermatology, Reference Centre for Mastocytosis (CEREMAST) Pitié-Salpêtrière Hospital, AP-HP, Sorbonne Université, Paris, France

^k Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany

^l Departments of Hematology and Pharmacology, Oslo University Hospital, Oslo, Norway

^m Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, Michigan

ⁿ Department of Internal Medicine and Immunology, Erasmus Medical Center, Rotterdam, The Netherlands

^o Guy's & St Thomas' NHS Foundation Trust, London, UK

^p Department of Medicine, University of Calgary, Calgary, Alberta, Canada

^q Section of Bone Marrow Transplantation and Cellular Therapy, Division of Hematology, Oncology and Cell Therapy, Department of Internal Medicine, Rush Medical College, Chicago, Illinois

^r Department of Immunology, Allergology, and Rheumatology, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium

^s Stanford Cancer Institute/Stanford University School of Medicine, Stanford, California

^t The Beatson West of Scotland Cancer Centre, Glasgow, Scotland

^u Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts

^v Department of Oncology, Hematology, and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

^w Department of Medicine, Karolinska Institutet, Huddinge, Sweden

^x Division of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics, University Hospitals Rainbow Babies and Children's Hospital; Case Western Reserve University School of Medicine, Cleveland, Ohio

^y Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah

^z Blueprint Medicines Corporation, Cambridge, Massachusetts

^aa Division of Allergy, Department of Dermatology, University Hospital Basel and University of Basel, Basel, Switzerland

^ab Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland

^ac Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland

^∗ Correspondence to: Karin Hartmann, MD, Division of Allergy, Department of Dermatology, University Hospital Basel and University of Basel, Burgfelderstrasse 101, Basel, 4055, Switzerland. Division of Allergy Department of Dermatology University Hospital Basel and University of Basel Burgfelderstrasse 101 Basel 4055 Switzerland

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.

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Key words : avapritinib, cutaneous mastocytosis, indolent systemic mastocytosis, KIT D816V inhibitor, PIONEER, skin lesion

Abbreviations used : AE, BSC, ISM, ISM-SAF, ITT, QoL, SD, SF-12, SM, TSS

Plan

Introduction

Methods

PIONEER study design

Skin lesion area and color assessment

Mast cell burden assessment in skin lesions

Patient-reported skin domain and individual symptom assessment

Safety

Study oversight and review

QoL in patients with skin involvement

Safety

Discussion

	Drs Siebenhaar and Broesby-Olsen contributed equally as co-first authors.
	Funding sources: Funding was received through the Blueprint Medicines Corporation .
	Patient consent: Patients provided written informed consent. We agree to keep the written and signed patient consent form together with the information about this manuscript on file in perpetuity and to provide that information to the journal as requested.
	IRB approval status: Approved by the institutional review board or independent ethics committee at each participating center.
	Data sharing statement: Requests for the study protocol or the anonymized derived data from this study that underlie the results reported in this article will be made available, beginning 12 months and ending 5 years following this article publication, to investigators who sign a data access agreement and provide a methodologically sound proposal to medinfo@blueprintmedicines.com .

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Vol 94 - N° 6

P. 1705-1713 - juin 2026 Retour au numéro

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Avapritinib improves cutaneous involvement in patients with indolent systemic mastocytosis: Results from the randomized, phase 2, interventional PIONEER study - 19/05/26

Abstract

Background

Objective

Methods

Results

Limitations

Conclusion

Plan

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