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

Abstract

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.