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.

Conclusion

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.


Continue Reading

Author Contributions

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.

References

1. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–578.

2. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351(4):337–345.

3. Hopps S, Medina P, Pant S, Webb R, Moorman M, Borders E. Cetuximab hypersensitivity infusion reactions: Incidence and risk factors. J Oncol Pharm Pract. 2013;19(3):222–227.

4. O’Neil BH, Allen R, Spigel DR, et al. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol. 2007;25(24):3644–3648.

5. Pirker R, Pereira JR, Szczesna A, et al. FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009;373(9674):1525–1531.

6. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116–1127.

7. Waqar SN, Tan BR, Zubal B, Kuperman DI, Adkins DR. Race and albuterol premedication are risk factors for hypersensitivity reactions to cetuximab. J Clin Oncol. 2008;26(suppl 15S): Abstract 9097.

8. Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med. 2008;358(11):1109–1117.

9. Mariotte D, Dupont B, Gervais R, et al. Anti-cetuximab IgE ELISA for identification of patients at a high risk of cetuximab-induced anaphylaxis. MAbs. 2011;3(4):396–401.

10. Patel DD, Goldberg RM. Cetuximab-associated infusion reactions: pathology and management. Oncology (Williston Park). 2006;20(11):1373–82; discussion 1382, 1392–84, 1397.

11. Hopps S, Medina P, Pant S, Webb R, Moorman M, Borders E. Cetuximab hypersensitivity infusion reactions: Incidence and risk factors. J Oncol Pharm Pract. 2013;19(3):222–227.

12. Grandvuillemin A, Disson-Dautriche A, Miremont-Salamé G, Fourrier-Reglat A, Sgro C.Réseau des Centres Régionaux de Pharmacovigilance Français. Cetuximab infusion reactions: French pharmacovigilance database analysis. J Oncol Pharm Pract. 2013;19(2):130–137.

13. Pointreau Y, Commins SP, Calais G, Watier H, Platts-Mills TA. Fatal infusion reactions to cetuximab: role of immunoglobulin e-mediated anaphylaxis. J Clin Oncol. 2012;30(3):334; author reply 335.

14. Tronconi MC, Sclafani F, Rimassa L, Carnaghi C, Personeni N, Santoro A. Fatal infusion reaction to cetuximab: the need for predictive risk factors and safer patient selection. J Clin Oncol. 2011;29(23):e680–681.

15. Ciccolini J, Gross E, Dahan L, Lacarelle B, Mercier C. Routine dihydropyrimidine dehydrogenase testing for anticipating 5-fluorouracil-related severe toxicities: hype or hope? Clin Colorectal Cancer. 2010;9(4):224–228.


Source: Libertas Academica.