Until now, no correlation between specific IgE levels and severity of allergic reactions to cetuximab has been shown.8,9 The unexpected finding of a possible correlation between a very high level of specific IgE and a fatal or near-fatal allergic reaction has prompted us to report our experience. In our report, all the patients had very elevated values of anticetuximab IgE, exceeding 250 AU. In comparison, the mean value in a previously reported cohort was 5 AU.9 Thus, highly increased values of anticetuximab IgE should be considered a possible contraindication for the use of cetuximab, as we did for the fourth patient described above. The precise cut-off point of anticetuximab IgE that defines this high-risk population remains to be determined. To date, with the cut-off value ,29 AU established in the previous work that permitted us to develop the anticetuximab IgE assay, the test had a negative predictive value of 98.5% and a positive predictive value was of 33.3%.9 The excellent negative predictive value suggests that when the test was negative, we can safely administer cetuximab. It was the priority of our team when we developed this test after the first case reported here. Given the positive predictive value for patients with a positive test, we can imagine performing another test such as an IDT with cetuximab, like in case 4, but this approach needs to be validated.
In the same way that screening for dihydropyrimidine dehydrogenase deficiency before using 5-fluorouracil has been recommended,15 systematic screening for the risk of severe hypersensitivity to cetuximab should be considered before using this product. Although hypersensitivity reactions to cetuximab are infrequent, we believe that screening for anticetuximab IgE is necessary, considering the potential severity of these reactions.
Conceived and designed the study: BD, DM, RG. Performed medical operations: DM, DL, MCV, CM. Analyzed the data: BD, JMG. Wrote the first draft of the manuscript: BD. Contributed to the writing of the manuscript: BD, DM, DL, RG. Agree with manuscript results and conclusions: BD, DM, DL, MCV, CM, RG. Jointly developed the structure and arguments for the paper: BD, DM, RG. Made critical revisions and approved final version: BD, DM, DL, RG. All authors reviewed and approved of the final manuscript.
Disclosures and Ethics
As a requirement of publication the authors have provided signed confirmation of their compliance with ethical and legal obligations including but not limited to compliance with ICMJE authorship and competing interests guidelines, that the article is neither under consideration for publication nor published elsewhere, of their compliance with legal and ethical guidelines concerning human and animal research participants (if applicable), and that permission has been obtained for reproduction of any copyrighted material. This article was subject to blind, independent, expert peer review. The reviewers reported no competing interests.
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Source: Libertas Academica.