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Previous Volume 358:1109-1117 March 13, 2008 Number 11 Next

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

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ABSTRACT

Background Cetuximab, 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.

Methods We 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.

Results Among 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--1,3-galactose, which is present on the Fab portion of the cetuximab heavy chain.

Conclusions In 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--1,3-galactose.

Source Information

From the Division of Hematology/Oncology, Department of Medicine (C.H.C., E.C., J.B., B.A.M.), the Department of Cancer Biology (C.H.C., R.J.S.), and the Department of Otolaryngology (R.J.S.), Vanderbilt University School of Medicine, Nashville; Bristol-Myers Squibb, Plainsboro, NJ (B.M., D.M.); Stanford University School of Medicine, Menlo Park, CA (Q.-T.L.); the Department of Medicine, Duke University Medical Center, Durham, NC (M.M.); Asthma and Allergic Diseases Center, University of Virginia, Charlottesville (S.M.S., J.H., T.A.E.P.-M.); ImClone Systems, Branchburg, NJ (Q.Z., D.J.H.); Channing Institute, Harvard University, Boston (D.G.); and Allergy and Asthma Clinic of Northwest Arkansas, Bentonville (T.H.).

Drs. Chung and Mirakhur contributed equally to this article.

Address reprint requests to Dr. Platts-Mills at the Asthma and Allergic Disease Center, University of Virginia Medical School, Box 801355, Charlottesville, VA 22908, or at tap2z{at}virginia.edu.

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