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Tyrosine Kinase Inhibitors for the Treatment of Mast Cell Diseases: Review and Update

Carpio-Escalona LV1, Prieto-García A2,3, Morales-Cabeza C4, Guilarte M5, Matito A6, Torrado I7, Vega-Castro A8,9, González-de-Olano D1

1Allergy Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
2Allergy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
3Instituto de Investigación Sanitaria Gregorio Marañón. CIBERER-U761
4Instituto Estudios de Mastocitosis Castilla La Mancha (CLMast), Virgen del Valle Hospital, Toledo, Spain
5Department of Allergy, Hospital Universitari Vall d’Hebron, VHIR (Vall d’Hebron Research Institute), Barcelona, Spain
6Allergy Department, Complejo Hospitalario Universitario de Toledo, Toledo, Spain
7Allergy Department, Hospital Universitario La Paz, Madrid, Spain
8Allergy Department, University Hospital of Guadalajara, Guadalajara, Spain
9Health Research Institute of Castilla la Mancha (IDISCAM), Castilla la Mancha, Spain

J Investig Allergol Clin Immunol 2025; Vol. 35(5)
doi: 10.18176/jiaci.1077

Mast cell diseases (MCDs) comprise several entities that are characterized by activation and/or proliferation of mast cells (MCs), leading to the appearance of cardinal symptoms. Such activation may be due to exaggerated functioning of MCs or to a mutation in a tyrosine kinase (usually the D816V mutation in KIT), which is a characteristic feature of systemic mastocytosis (SM) and/or clonal MC activation syndromes. Depending on the MC burden and tissue infiltration, SM can be classified as advanced or nonadvanced. Traditionally, the treatment of MCDs has been based on best supportive care. In cases of advanced SM that responds poorly to best supportive care, management can also take the form of non–target-directed cytoreductive treatment, administration of monoclonal antibodies, targeted therapies, and even bone marrow transplantation. The advance of personalized medicine has led to the emergence of new and more specific tyrosine kinase inhibitors (TKIs), which achieve greater symptom control and improve disease course, sometimes leading to remission. In recent years, clinical trials have been carried out to evaluate the effectiveness of some of these TKIs in nonadvanced forms of mastocytosis, with eventual approval for this subtype in some cases. TKIs represent a major advance in the management of MCDs, with more patients being able to benefit from a treatment that addresses pathophysiology. We review the main TKIs currently available for SM, their indications, and their safety and effectiveness.

Key words: Avapritinib, Bezuclastinib, Elenestinib, Imatinib, Masitinib, Mast cell, Mastocytosis, Midostaurin