KIT-Targeting Drugs in the Management of Nonadvanced and Advanced Systemic Mastocytosis.

Abstract

Systemic mastocytosis (SM) is a rare hematological neoplasm driven by the KIT D816V mutation in up to 95% of cases. SM is classified into nonadvanced SM-comprising indolent SM (ISM), bone marrow (BM) mastocytosis, and smoldering SM-and advanced SM (AdvSM), with the subtypes aggressive SM, SM with an associated hematological neoplasm (SM-AHN according to the World Health Organization), and mast cell (MC) leukemia. Clinical presentations are heterogeneous, and careful evaluation of clinical and laboratory parameters is required to plan patient management. Here we discuss the diagnosis and treatment of 2 patients with KIT D816V positive SM, 1 with AdvSM and 1 with ISM, both of whom received KIT-targeted therapies. In addition to clinical presentations caused by a combination of MC mediator symptoms and consequences from MC infiltration of different organ systems, the diagnostic workup included qualitative and quantitative assessment of variably affected key parameters from (1) peripheral blood (eg, blood counts, serum tryptase, and other serum markers; variant allele frequency [VAF] of KIT D816V; and additional somatic mutations); (2) BM MC infiltration, KIT D816V VAF, presence/absence of an AHN/associated myeloid neoplasm, and cytogenetic analysis; and (3) organ infiltration/dysfunction (primarily affecting skin, bone/BM, and visceral organs).