Avapritinib achieves long-term disease control with favorable safety in patients with indolent systemic mastocytosis over 3 years

Year: 2026

Type: article

Abstract: BACKGROUND: Indolent systemic mastocytosis (ISM), a clonal mast cell disease primarily driven by the KIT D816V mutation, can cause long-term debilitating symptoms and poor quality of life. Most patients rely on symptom-directed best supportive care (BSC) medications, which do not treat the underlying driver of ISM. Avapritinib, an oral, potent, selective KIT D816V inhibitor, is approved in adults with ISM. OBJECTIVE: We sought to understand the long-term efficacy and safety of avapritinib in ISM. METHODS: The PIONEER trial (NCT03731260) enrolled adults with moderate to severe ISM symptoms. Patients initiated avapritinib 25 mg once daily (QD; recommended dose) plus BSC in part 1, 2, or 3; open-label part 3 is ongoing with up to 5 years of follow-up. As per investigator discretion and disease burden, a dose increase up to avapritinib 50 mg QD was permitted in part 3. RESULTS: As of February 21, 2025, 226 patients initiated avapritinib at 25 mg QD. The median (range) treatment duration was 40.0 (0.7-67.2) months. Patients receiving avapritinib experienced durable and clinically meaningful symptom improvement (mean change, -19.39 [n = 127] in the Indolent Systemic Mastocytosis Symptom Assessment Form total symptom score) through approximately 3 years. Avapritinib continued to be well tolerated for a longer term with a safety profile comparable with the previously reported placebo-controlled portion. Most treatment-related adverse events (TRAEs) were grades 1 to 2, with limited grade 3 or higher reported. Edema events were the most frequent TRAEs (mostly grade 1). Serious TRAEs occurred in 3 patients (1%), and 7 patients (3%) discontinued treatment because of TRAEs. CONCLUSIONS: Long-term follow-up (median, ∼3 years) demonstrates that avapritinib is effective and well tolerated. Avapritinib shows a favorable benefit-risk profile as a chronic ISM treatment.

Source: Journal of Allergy and Clinical Immunology

DOI: 10.1016/j.jaci.2026.04.001

Institutions: University of Michigan, University of Antwerp, Antwerp University Hospital, Stanford Cancer Institute, Stanford University, Universitätsklinikum Aachen, RWTH Aachen University, Hospital Virgen del Valle, Guy's and St Thomas' NHS Foundation Trust, Centre Hospitalier Universitaire de Toulouse, Columbia University Irving Medical Center, Columbia University, University Medical Center Groningen, University of Groningen, Erasmus MC, University of Calgary, Oslo University Hospital, Heidelberg University, University Medical Centre Mannheim, Mayo Clinic, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Rush University Medical Center, Rush University, University Medical Center Hamburg-Eppendorf, St. Michael's Hospital, University of Toronto, The University of Texas MD Anderson Cancer Center, Dana-Farber Cancer Institute, Duke University, University of Alabama at Birmingham, University of Salerno, Azienda Ospedaliera Universitaria Integrata Verona, University of Basel, University Hospital of Basel, Odense University Hospital, Uppsala University, Uppsala University Hospital, University of Utah, Stanford Medicine, Brigham and Women's Hospital, Harvard University, Humboldt-Universität zu Berlin, Fraunhofer Institute for Translational Medicine and Pharmacology, Freie Universität Berlin, Charité - Universitätsmedizin Berlin, Blueprint Medicines (United States), Huntsman Cancer Institute

Language: English

Topic: Mast cells and histamine

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,900

OpenAlex ID: W7154304185