Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose.

Published

Journal Article

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-alpha-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-alpha-1,3-galactose.

Full Text

Duke Authors

Cited Authors

  • Chung, CH; Mirakhur, B; Chan, E; Le, Q-T; Berlin, J; Morse, M; Murphy, BA; Satinover, SM; Hosen, J; Mauro, D; Slebos, RJ; Zhou, Q; Gold, D; Hatley, T; Hicklin, DJ; Platts-Mills, TAE

Published Date

  • March 13, 2008

Published In

Volume / Issue

  • 358 / 11

Start / End Page

  • 1109 - 1117

PubMed ID

  • 18337601

Pubmed Central ID

  • 18337601

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa074943

Language

  • eng

Conference Location

  • United States