An abstract recently published in the Journal of Allergy and Clinical Immunology found that patients with indolent systemic mastocytosis (ISM) may respond to avapritinib even if they don’t have KIT gene mutations detectable via droplet digital polymerase chain reaction (ddPCR).
The majority of patients with ISM have a mutation in the KIT gene, which codes for a protein that plays a role in mast cell growth and survival. In fact, over 90% of individuals with SM have the D816V mutation, in which the amino acid aspartic acid at position 816 in the protein is replaced with the amino acid valine.
ddPCR is a common tool used to detect genetic mutations in patients with SM. However, some patients who undergo genetic testing with ddPCR do not have detectible mutations. Thus, the study’s authors sought to determine if a more sensitive technology called duplex sequencing (DS) can be used to identify additional patients with KIT mutations who respond to avapritinib.
The PIONEER clinical trial demonstrated the efficacy of avapritinib, an inhibitor of KIT D816V. The study’s authors included 246 individuals with ISM who participated in the PIONEER trial. Of these participants, 209 had KIT D816V mutations detectable by ddPCR, 26 had KIT mutations detectable through DS but not ddPCR and 11 had no detectable KIT mutations with either tool.
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The authors found that among the 26 patients with detectable mutations by DS, total symptom score decreased by 30.7%, on average, after six months of treatment with avapritinib. Additionally, serum tryptase levels, a common biomarker of SM, declined after treatment.
“Avapritinib can reduce ISM symptoms even when KIT mutations are undetectable by ddPCR in [peripheral blood],” the authors concluded. “This may be explained by our finding that, in PIONEER, 70% of patients with undetectable KIT D816V by ddPCR had KIT mutations, including non-D816V mutations, detected by DS.”
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