Correspondence

Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose

N Engl J Med 2008; 358:2735-2736June 19, 2008

Article

To the Editor:

Chung and colleagues (March 13 issue)1 found IgE antibodies to galactose-α-1,3-galactose in pretreatment serum samples from 17 of 25 patients who had hypersensitivity reactions to cetuximab, whereas IgE antibodies were found in only 1 of 51 patients who did not have a hypersensitivity reaction. If, as suggested, the presence of such antibodies in pretreatment samples is predictive of anaphylaxis, pretreatment testing would help in minimizing the risk of anaphylaxis associated with cetuximab. It would be important to know whether skin testing was done in the study patients, and if so, whether the results were concordant with the presence of IgE antibodies to cetuximab.

Dilani F. Arnold, M.R.C.P.
Siraj A. Misbah, F.R.C.P., F.R.C.Path.
John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
dilani_arnold@yahoo.co.uk

1 References

1. 1

   Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-α-1,3-galactose. N Engl J Med 2008;358:1109-1117
   Full Text | Web of Science | Medline

Author/Editor Response

The patients with cancer had been treated with cetuximab before we were aware of the relevance of IgE antibodies to galactose-α-1,3-galactose and were not available for skin testing. Some of the patients who presented with delayed anaphylaxis after eating beef, pork, or lamb have undergone skin testing with mammalian proteins and cetuximab itself.1 Despite skin-prick testing with 100 μg of cetuximab, the wheal size was not predictive of the serum titer IgE antibodies to galactose-α-1,3-galactose. The absence of significant skin responses to similar testing in patients receiving cetuximab (Kulczycki A: personal communication) may reflect the low affinity of binding of antibodies to uncharged carbohydrates.2 We believe that a blood test for IgE specific for the oligosaccharide on cetuximab would be the easiest and most reliable screening test. Any plan for screening will also have to factor in the geographic area that needs to be covered.3

Scott P. Commins, M.D., Ph.D.
University of Virginia, Charlottesville, VA 22908

Beloo Mirakhur, M.D., Ph.D.
Bristol-Myers Squibb, Plainsboro, NJ 08536-1615

Thomas A.E. Platts-Mills, M.D., Ph.D.
University of Virginia Medical School, Charlottesville, VA 22908
tap2z@virginia.edu

3 References

1. 1

   Commins SP, Lucas S, Hosen J, et al. Anaphylaxis and IgE antibodies to galactose-alpha-1,3-galactose (alphaGal): insight from the identification of novel IgE antibodies to carbohydrates on mammalian proteins. Presented at the American Academy of Allergy, Asthma, and Immunology Annual Meeting, Philadelphia, March 14–18, 2008.
   

2. 2

   Macher BA, Galili U. The Galα1,3Galβ1,4GlcNAc-R (α-Gal) epitope: a carbohydrate of unique evolution and clinical relevance. Biochim Biophys Acta 2008;1780:75-88
   CrossRef | Web of Science | Medline

3. 3

   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;25:3644-3648
   CrossRef | Web of Science | Medline

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