Abstract: Hypersensitivity reactions are a classic side effect of cetuximab. We report the cases of three patients who developed life-threatening hypersensitivity to cetuximab, which could have been predicted by assessing the concentration of serum anticetuximab immunoglobulin (Ig)E. The anticetuximab IgE concentration could be an interesting test to predict which patients are at risk of experiencing severe hypersensitivity reactions to cetuximab.
Keywords: hypersensitivity, anaphylaxis, cetuximab, antidrug IgE, neoplasms
Citation: Dupont et al. Case Report About Fatal or Near-Fatal Hypersensitivity Reactions to Cetuximab: Anticetuximab IgEas a Valuable Screening Test. Clinical Medicine Insights: Oncology 2014:8 91–94 doi: 10.4137/CMO.S13897.
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Received: December 12, 2013. Resubmitted: February 27, 2014. Accepted for publication: February 28, 2014.
Academic editor: William C.S. Cho, Editor in Chief
TYPE: Case Report
Funding: Authors disclose no funding sources.
Competing Interests: Authors disclose no potential conflicts of interest.
Copyright: © the authors, publisher and licensee Libertas Academica Limited. This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.
Correspondence: [email protected]
Introduction
Hypersensitivity reactions are a classic side effect of cetuximab. The frequency of severe reactions varies from 1.2%–22%.1–6 No clinical criteria (previously reported to be associated with a risk of hypersensitivity to cetuximab) is so strong that it can predict patients at risk of hypersensitivity reaction.4,7 However, a strong correlation between the occurrence of hypersensitivity reactions to cetuximab and the presence of anticetuximab immunoglobulin (Ig)E in the sera of patients before an initial injection of cetuximab has been demonstrated.8,9 The anticetuximab IgE concentration could be an interesting test to predict which patients are at risk of severe hypersensitivity reactions to cetuximab. We have previously developed a reliable and reproducible anticetuximab IgE assay using enzyme-linked immunosorbent assay (ELISA).9
We report the cases of patients living in Normandy (France) who developed life-threatening hypersensitivity to cetuximab, which could have been predicted by assessing the concentration of serum anticetuximab IgE.
Materials and Methods
Anti-cetuximab IgEs were measured using an enzyme-linked immunosorbent assay (ELISA). Polystyrene microtiter plates (Maxisorp Nunc, Roskilde, Denmark) were coated with 100 μL of a 0.5 μg/L cetuximab solution (Erbitux® , Merck Serrano) in phosphate buffered saline (PBS), overnight at 4 °C. After three washes with PBS containing Tween-20 (0.1%), plates were saturated with a solution of human albumin (0.1%) for 2 h at 37 °C. Duplicate serum samples (diluted 1/25) were added and incubated overnight at 4 °C. Bound anti-cetuximab IgE antibodies were detected using a biotinylated rat monoclonal anti-human-IgE (LO-HE-17, P.A.R.I.S, Compiègne, France), allowed to react for 1.5 h at 37 °C. Streptavidin-alkaline phosphatase Beckman Coulter, Fullerton, USA, 1/2,000 dilution, was added, followed by 1 mg/mL paranitrophenyl phosphate solution (PNPP, Interchim, Montluçon, France). Positive samples were titrated after serial dilutions from 1/50 to 1/200 or more as appropriate. Optical density (OD) was measured at 450 nm (Elx808, KC4 software, Bio-Tek) and the mean of duplicates was calculated. Results were expressed in arbitrary units of IgE (AU) using a positive serum sample from a healthy donor as a standard.
To assess the specificity of the detection, a competition ELISA was performed on sera diluted 1/25 using an excess of cetuximab or an IgG1 isotype control (rituximab, Mabthera®) or a G1 m3 allotype control (basiliximab, Simulect®), at 1.1 mg/mL final concentration.
