The Effect of Bezuclastinib on the Pathobiology of Mastocytosis: Changes in BM Mast Cells, Tryptase, and KIT p.D816V Variant Allele Frequency From the Pivotal Summit Trial

Tracy I. George. MD discusses how in the phase 2 SUMMIT trial, bezuclastinib, a selective KIT p.D816V inhibitor, demonstrated significant disease-modifying activity in non-advanced systemic mastocytosis, with marked reductions in bone marrow mast cell burden, normalization of mast cell phenotype (CD25/CD30), and deep decreases in KIT p.D816V variant allele frequency and serum tryptase. By Week 24, over half of treated patients no longer met WHO diagnostic criteria and the majority achieved a pure pathologic response that correlated with meaningful symptom improvement, supporting bezuclastinib’s potential to transform underlying disease biology.