Tyrosine Kinase Inhibitors in Non-advanced Systemic Mastocytosis

Abstract

Systemic mastocytosis is associated with KIT D816V mutation in more than 90% of cases. Patients with non-advanced forms of mastocytosis (indolent systemic mastocytosis, bone marrow mastocytosis, and smoldering systenic mastocytosis) have a low rate of progession to advanced variants and generally have a comparable life expectancy to age-matched general population. Symptomatology in non-advanced mastocytosis is variable and is related to mast cell mediator release. While some patients require no or minimal symptomatic therapy with antimediator drugs, other may suffer from refractory symptoms impacting the quality of life despite being on multiple anti-mediator drugs. KIT tyrosine kinase inhibitors have been approved for advanced SM, and avapritinib has also been recently approved as the first such inhibitor for indolent systemic mastocytosis. Other TKIs are currently in clinical trials for patients with non-advanced SM who have persistent and severe symptoms despite optimized antimediator therapy. This article will review the current state of the science and available clinical data from trials of tyrosine kinase inhibitors in non-advanced systemic mastocytosis.

Keywords: Avapritinib; Imatinib; KIT D816V mutation; Mastocytosis; Midostaurin; Tyrosine kinase inhibitors.