Year: 2026
Type: article
Abstract: Background: Patients with indolent systemic mastocytosis (ISM), a clonal mast cell disease primarily driven by the KIT D816V mutation, often have lifelong debilitating symptoms. Anaphylaxis is a common feature of the disease seen in up to half of patients. The effects of KIT D816V-targeted therapy on the incidence of anaphylaxis are unknown. Methods: We describe anaphylaxis events occurring in the study population of PIONEER (NCT03731260) during the 12-week screening and/or 24-week treatment period. This study had previously demonstrated the efficacy and safety of the oral, highly selective, KIT D816V inhibitor avapritinib compared with placebo in patients with moderate-to-severe ISM. Results: In total, 13/212 (6.1%) patients in PIONEER experienced anaphylaxis during screening or treatment (6 during screening, 5 during treatment, and 2 during both screening and treatment). Baseline demographics, clinical characteristics, and known triggers varied. During the randomized, placebo-controlled treatment period, 4/141 (2.8%) avapritinib-treated patients and 3/71 (4.2%) placebo-treated patients experienced anaphylaxis. Conclusions: Larger studies with longer-term follow-up are required to further confirm the effects of avapritinib on anaphylaxis in patients with SM.
Authors: Thanai Pongdee, Mariana Castells, Cem Akin, Ingunn Dybedal, Jason Gotlib, Jens Peter Panse, Ivan Alvarez-Twose, Cristina Morales Cabeza, Sonia Cerquozzi, Peter Vadas, Vidushi Swarup, Pankit Vachhani, Friederike Wortmann, Cecilia Arana Yi, Ilda Bidollari, Kate Newberry, Daniel Shaheen, Karin Hartmann
Institutions: Mayo Clinic, Brigham and Women's Hospital, Harvard University, University of Michigan, Oslo University Hospital, Stanford Medicine, Stanford Cancer Institute, Stanford University, Universitätsklinikum Aachen, RWTH Aachen University, Servicio de Salud de Castilla La Mancha, Hospital Virgen del Valle, University of Calgary, St. Michael's Hospital, University of Alabama at Birmingham, O'Neal Comprehensive Cancer Center, University of Lübeck, Mayo Clinic in Arizona, 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: gold
Estimated APC paid: $3,508
Funder: Sanofi
OpenAlex ID: W7135236222