• Christine H Chung, Beloo Mirakhur, Emily Chan, Quynh-Thu Le, Jordan Berlin, Michael Morse, Barbara A Murphy, Shama M Satinover, Jacob Hosen, David Mauro, Robbert J Slebos, Qinwei Zhou, Diane Gold, Tina Hatley, Daniel J Hicklin, and Thomas A E Platts-Mills.
• Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, USA.
• N. Engl. J. Med. 2008 Mar 13; 358 (11): 1109-17.

BackgroundCetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, is approved for use in colorectal cancer and squamous-cell carcinoma of the head and neck. A high prevalence of hypersensitivity reactions to cetuximab has been reported in some areas of the United States.MethodsWe analyzed serum samples from four groups of subjects for IgE antibodies against cetuximab: pretreatment samples from 76 case subjects who had been treated with cetuximab at multiple centers, predominantly in Tennessee, Arkansas, and North Carolina; samples from 72 control subjects in Tennessee; samples from 49 control subjects with cancer in northern California; and samples from 341 female control subjects in Boston.ResultsAmong 76 cetuximab-treated subjects, 25 had a hypersensitivity reaction to the drug. IgE antibodies against cetuximab were found in pretreatment samples from 17 of these subjects; only 1 of 51 subjects who did not have a hypersensitivity reaction had such antibodies (P<0.001). IgE antibodies against cetuximab were found in 15 of 72 samples (20.8%) from control subjects in Tennessee, in 3 of 49 samples (6.1%) from northern California, and in 2 of 341 samples (0.6%) from Boston. The IgE antibodies were shown to be specific for an oligosaccharide, galactose-alpha-1,3-galactose, which is present on the Fab portion of the cetuximab heavy chain.ConclusionsIn most subjects who had a hypersensitivity reaction to cetuximab, IgE antibodies against cetuximab were present in serum before therapy. The antibodies were specific for galactose-alpha-1,3-galactose.Copyright 2008 Massachusetts Medical Society.

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