When systemic mastocytosis co-occurs with an associated myeloid neoplasm and is driven by the KIT D816V mutation, it constitutes a distinct advanced-disease category — SM-AMN — that requires a specifically tailored treatment strategy.
This protocol addresses patients with systemic mastocytosis with an associated myeloid neoplasm (SM-AMN) harboring a confirmed KIT D816V mutation. Treatment of SM-AMN primarily targets the myeloid neoplasm component, with particular urgency when an aggressive myeloid disease such as acute leukemia is present alongside the mastocytosis.
The primary objectives are reversion of disease-related organ damage and a marked decrease in bone marrow mast cell burden. Potent agents that selectively target mutant-KIT have demonstrated the potential for molecular remissions, suggesting the possibility of a disease-modifying therapeutic effect.
The current first-line standard of care for SM-AMN with KIT D816V involves an FDA-approved oral agent that selectively targets the mutant-KIT driver — the first such agent to receive regulatory approval specifically for advanced systemic mastocytosis, including the SM-AMN subtype. Regulatory approval was based on data from prospective clinical trials. The complete regimen, monitoring parameters, and sequencing details are available in the full structured protocol.
DOI: 10.1002/ajh.26962