Nationwide pharmacovigilance data for cetuximab-induced anaphylaxis and predictive model validation using prospective specific IgE detection

Cetuximab (chimeric monoclonal antibody to human epidermal growth factor receptor) is used to treat colorectal and head and neck cancers. Due to cross-reactivity with galactose-α-1,3-galactose (alpha-gal), it can induce hypersensitivity even at first administration. We aimed to determine the incidence and clinical manifestation of cetuximab-induced anaphylaxis, and to establish a means of predicting its incidence in patients ahead of treatment. Nationwide and single-center pharmacovigilance data from 2010 to 2017 were collected from the Korea Institute of Drug Safety-Korea Adverse Event Reporting System and Severance Regional Pharmacovigilance Center. Patients scheduled for cetuximab administration were enrolled prospectively. A skin prick test was carried out and serum IgE specific to cetuximab and cross-reactive allergens were measured. Reactions were monitored after cetuximab infusion. Over 8 years, there were 23 reports of anaphylaxis nationwide. In a single-center study, incidence of cetuximab-induced anaphylaxis was 1.1%. Most anaphylaxis occurred at first injection (93.3%), even under pretreatment with anti-allergic drugs. Four of 64 patients (6.3%) experienced severe anaphylaxis. The median cetuximab-specific IgE titer was 6.9 kUA/L in patients experiencing anaphylaxis and 0 kUA/L in those who did not (P