Patients with systemic mastocytosis (SM) and venom allergies may face increased risks during immunotherapy due to the presence of a genetic variant known as KIT p.D816V, according to results from a study published recently in Clinical and Translational Allergy.
Patients undergoing honeybee venom immunotherapy faced a significantly higher risk of systemic adverse events if they carried the KIT p.D816V mutation, the study found.
What is SM?
Systemic mastocytosis (SM) is a rare hematological disease characterized by mast cells that are overactive and accumulate in different parts of the body such as the bone marrow, liver, spleen, gastrointestinal tract and lymph nodes.
“Importantly, half of the KIT p.D816V‐positive patients who received honeybee VIT [venom immunotherapy] experienced SAEs [systemic adverse events] during treatment,” study authors said.
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“Furthermore, KIT p.D816V was associated with VIT failure in one‐third of the patients overall, and it was a positive predictor of wasp VIT failure,” they added. “These observations emphasize the importance of KIT p.D816V screening before starting honeybee and wasp VIT and the need for detailed monitoring of high‐risk patients during VIT build‐up and after VIT completion.”
A recent study of 839 patients undergoing venom immunotherapy found that 15% carried the mutation in their peripheral blood leukocytes. These individuals were more likely to experience severe systemic reactions during treatment, particularly with honeybee venom. In addition, the presence of KIT p.D816V was a strong predictor of treatment failure in patients undergoing wasp venom immunotherapy.
This study used a highly sensitive quantitative PCR test to detect KIT p.D816V in patients receiving venom immunotherapy for honeybee or wasp venom allergies.
Among those tested, 125 patients had detectable levels of the mutation. Importantly, most of the individuals (70%) had normal levels of basal serum tryptase, a commonly used but insufficient marker for identifying underlying mast cell disorders. The finding underscored the need for routine genetic screening, as normal levels of basal serum tryptase alone do not rule out a higher risk of severe allergic reactions.
Nearly half (48%) of the KIT-positive patients experienced systemic adverse events, compared to 28% of those without the mutation. The severity of the reactions was linked to a higher allele burden of KIT p.D816V, with most affected patients having a burden exceeding 0.01%. In contrast, systemic adverse events were much rarer in patients receiving wasp venom immunotherapy, regardless of their KIT status.
Beyond acute reactions during treatment, the presence of KIT p.D816V also influenced long-term treatment success. Patients with the mutation had a significantly higher likelihood of experiencing venom immunotherapy failure, meaning they remained at risk for severe allergic reactions to insect stings even after completing treatment. This was particularly pronounced in wasp venom immunotherapy, where KIT p.D816V was a strong predictor of treatment failure, with an odds ratio of over 3.5 in multivariate analysis.
The results highlighted the critical role of genetic testing in managing patients with venom allergies. By identifying those at higher risk, physicians can tailor treatment strategies to improve safety and effectiveness. Screening for KIT p.D816V could help guide decisions on the type of venom used in immunotherapy, monitoring protocols, and the need for extended treatment durations.
For patients, this could mean a more personalized approach to allergy treatment. Those found to carry the KIT p.D816V mutation may require closer observation, alternative treatment strategies or extended immunotherapy to reduce their risk of severe reactions. As research advances, incorporating genetic testing into standard allergy care may offer improved outcomes for individuals with venom-induced anaphylaxis.
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