Tebyan Khalfalla BSa, Kareena S. Garg BSb, S. Minhaj Rahman MDa,d, Aamir N. Hussain MD MAPPc
aUniversity of Rochester School of Medicine, Rochester, NY
bGeorgetown University School of Medicine, Washington, DC
cGalaria Plastic Surgery and Dermatology, Chantilly, VA
dDermatology, University of Connecticut Health Center, Farmington, CT
Abstract
Background: Mastocytoses, a category of diseases characterized by the clonal proliferation of mast cells and the release of their mediators, can be broadly classified as systemic mastocytosis (SM), cutaneous mastocytosis (CM), or mast cell sarcoma (MCS), with treatment options and prognoses varying based on subtype. Advancements in biologics and genetic testing have increased the variety of therapeutic options for mastocytoses. This paper characterizes the therapeutic landscape for mastocytoses with a focus on biologics and other novel medications.
Methods: A comprehensive literature search of PubMed and Scopus databases was conducted from the inception of the databases to January 31, 2024. Search terms included "[disease state] AND [biologic class]" or "[disease state] AND [biologic name]".
Results: Of the 672 screened articles, 55 met the following inclusion criteria: (1) diagnosis of either CM, SM, or MCS, and (2) treatment with one of the following biologic regimens: tyrosine kinase inhibitor (TKI) (including a JAK/STAT inhibitor (JAK1/2i), or a monoclonal antibody). Treatment led to successful resolution of the disease or reduction of symptoms in 90% of the patients using TKIs (n=698), including all patients (n=4) using the JAK1/2i ruxolitinib alone, and 90.6% (n=125) using monoclonal antibodies.
Conclusion: Successful treatment or symptom improvement of SM, CM, and MCS has been demonstrated through the use of JAK1/2i, TKI, and monoclonal antibodies. More studies are needed to characterize JAK1/2i regimens as clinical trials are lacking.
INTRODUCTION
Mastocytosis refers to a group of disorders in which clonal mast cells proliferate and accumulate in various organs, triggering different physiologic responses. The disease is divided into 3 main categories: systemic mastocytosis (SM), cutaneous mastocytosis (CM), and mast cell sarcoma (MCS) (Table 1). The prevalence of mastocytosis is estimated to be 1 in 10,000, with the incidence being approximately 1 in 100,000 per year, with 65% of cases presenting in pediatric populations.1 The disease is believed to be driven by a mutation in the c-kit proto-oncogene (KIT), which encodes the KIT protein. Proliferation of mast cells is driven by stem cell factor (SCF) protein binding to its receptor, KIT. With the c-kit mutation, there can be an activating mutation, ligand-independent activation, or suppression of protein apoptosis that drives the proliferation of mast cells we see in mastocytosis.2 Interestingly, somatic gain of function mutation in the KIT gene, D816V exon 17, is found in over 80% of those with adult-onset mastocytosis, highlighting the role of KIT mutations in the pathogenesis of the disease. However, studies have shown that this is not the case for pediatric populations, as around 86% of children did not exhibit this mutation in 1 study.3 These genetic pathophysiologic differences illustrate the importance of correctly identifying the mutation present in order to help curate targeted therapeutic regimens.
