Prevalence of KIT D816V in anaphylaxis or systemic mast cell activation

The KIT D816V mutation is a hallmark of clonal mast cell disease (cMCD) including systemic mastocytosis. cMCD diagnosis is frequently delayed because of variable symptoms until confirmatory bone marrow biopsy is performed. Screening techniques for KIT D816V variant in peripheral blood (PB) may facilitate diagnosis. Prevalence of KIT D816V in patients with anaphylaxis or mast cell activation (MCA) symptoms is unknown.

We sought to determine the prevalence of KIT D816V in PB of patients with anaphylaxis or systemic MCA symptoms.

The PROSPECTOR trial (NCT04811365) included patients with anaphylaxis or systemic MCA symptoms who had (1) moderate to severe anaphylaxis to Hymenoptera sting, (2) 20% + 2 ng/mL increase in tryptase level over the baseline level during moderate to severe anaphylaxis with cardiovascular involvement, and/or (3) involvement of both the cardiovascular system and 1 or more other organ systems with basal serum tryptase (BST) levels greater than or equal to 8 ng/mL. KIT D816V in PB, hereditary α-tryptasemia (HaT), and BST levels were centrally evaluated.

Of the 381 enrolled patients, 179, 76, and 203 were in groups 1, 2, and/or 3, respectively. Fifteen patients (4%) had detectable KIT D816V in PB; 12 of 15 (80%) had BST levels less than 20 ng/mL. Most patients with KIT D816V (11 of 15 [73%]) had Ring-Messmer grade III/IV anaphylaxis. Fourteen additional patients with BST levels greater than 11.4 ng/mL, no HaT, and local follow-up were diagnosed with cMCD, totaling 29 of 381 patients (8%) with cMCD in the PROSPECTOR trial. The overall prevalence of HaT was 36% (138 of 381).

The PROSPECTOR trial demonstrated a meaningful KIT D816V prevalence in patients with anaphylaxis or systemic MCA symptoms; more frequent and sensitive screening for KIT D816V is needed in this patient population.