Fatal Infusion Reactions to Cetuximab: Role of Immunoglobulin E–Mediated Anaphylaxis
Source: Journal of Clinical Oncology To the Editor: In Journal of Clinical Oncology, Tronconi et al1 report a fatal hypersensitivity reaction to cetuximab in a 63-year-old patient with metastatic colon cancer and outlined a 0.1% incidence of death in the literature. We greatly acknowledge the authors' desire to communicate the risk of fatal anaphylactic reaction with cetuximab. Over the past 2 years in our center in Tours, France, four instances of grade 4 anaphylactic reactions occurred in patients treated for head and neck cancer (locally advanced or metastatic), with one immediately fatal; another patient died within 5 days (unpublished data). Seven lethal anaphylactic reactions were registered in a pharmacovigilance survey in France, based on spontaneous declarations (Grandvuillemin et al, manuscript in preparation). Anaphylaxis to cetuximab is a problem that merits serious clinical attention. In the authors' words, “the pathogenic mechanisms underlying the development of this phenomenon remain to be elucidated.”1 They raise the hypothesis of immunoglobulin E (IgE) –independent mechanisms, even in the context of a paradoxic atopic history. Moreover, Tronconi et al suggest that the field “search for reliable risk factors that can facilitate the safe selection of patients as candidates for cetuximab-based treatment.”1 These comments are quite surprising, because they do not integrate major contributions that have been previously published. Indeed, it has been known for 3 years that anaphylaxis to cetuximab is the result of antidrug IgE antibodies present in patient serum before therapy.2 These IgE antibodies are directed against galactose-α-1, 3-galactose (α3Gal) residues, present in the [...]