Novel Approaches for Systemic Mastocytosis

Abstract

Purpose of review: The purpose of this review is to summarize the pathophysiology of systemic mastocytosis, review the most recent clinical trials and drug development in systemic mastocytosis, with a specific focus on the advanced systemic mastocytosis subtypes.

Recent findings: Systemic mastocytosis is a clonal neoplasm of mast cells that has had a number of successful therapeutic options being developed in the past few years. The first therapeutic agent to be Food and Drug Administration (FDA) approved in decades was midostaurin in 2017 with a 60% response rate % with improvement in both end-organ damage and symptoms. However, complete responses/remissions with midostaurin have been elusive. Additional clinical trials of tyrosine kinase inhibitors that target the proto-oncogene receptor tyrosine kinase (KIT) mutation show great promise. The two drugs with promising early clinical trial data include avapritinib and DCC-2618 with avapritinib showing potential to induce complete remissions.

Summary: Therapies for systemic mastocytosis are in a stage of evolution with further elucidation of additional mutations associated with oncogenesis in addition to the most commonly described KIT (give details), ongoing clinical trials could potentially with lead to further targeted therapy and increased complete responses and durable remissions.