title: Anti-cetuximab IgE ELISA for identification of patients at a high risk of cetuximab-induced anaphylaxis.
abstract: Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3-4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p=0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3-4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.
authors.affiliation: Laboratoire d'Immunologie et Immunopathologie, Centre Hospitalier Universitaire, Caen, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Mariotte
authors.forename: Benoît
authors.initials: B
authors.lastname: Dupont
authors.forename: Radj
authors.initials: R
authors.lastname: Gervais
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Galais
authors.forename: Dominique
authors.initials: D
authors.lastname: Laroche
authors.forename: Aurore
authors.initials: A
authors.lastname: Tranchant
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Comby
authors.forename: Karine
authors.initials: K
authors.lastname: Bouhier-Leporrier
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Reimund
authors.forename: Brigitte
authors.initials: B
authors.lastname: Le Mauff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000707:Anaphylaxis / Q000139:chemically induced* / Q000517:prevention & control; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011237:Predictive Value of Tests; D012306:Risk; D012680:Sensitivity and Specificity
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C026408:anti-IgE antibodies; D000068818:Cetuximab