Cetuximab is a chimeric mouse-human monoclonal antibody biologic used for the treatment of epidermal growth factor receptor-positive colorectal cancer and head and neck cancer. The incidence of severe anaphylaxis after infusion of cetuximab is a rare but fatal complication. Galactose-α-1,3-galactose (α-gal), a side-chain component in cetuximab, can cause the α-gal syndrome, an allergic cross-reaction to the α-gal contained in mammalian muscle. Here, we report a case of cardiac arrest induced by an anaphylactic reaction from cetuximab infusion. After the initial dosing of cetuximab in an outpatient setting, the patient developed sudden cardiac arrest. Flushing of the skin and bronchoconstriction led to the diagnosis of a severe anaphylactic reaction, whereupon he was treated with repeated doses of epinephrine, steroids, and continuous epinephrine infusion. The patient responded well to initial treatment, leading to a full recovery. The patient's history and subsequent blood tests did not show any meat allergies. As an increasing number of patients receive chemotherapy as outpatients, it is important to be aware of the possibility of severe allergic reactions induced by these drugs.
Iwamoto T, Okamoto A, Ishinaga H, Shimizu K, Gayle AA, et al.
Cancer medicine •
Cetuximab is remarkable for the relatively high rate and severity of hypersensitivity reactions (HR) being reported in the literature. Screening for cetuximab-specific IgE in serum via immunoassay has been found to be useful in preventing HR; however, these tests are known to have a low positive predictive rate. In an attempt to remedy this, we evaluated the interaction between cetuximab and IgE on basophils for predicting severe cetuximab-induced HR. Twelve head and neck cancer patients were enrolled in this single-institution study: four with a history of cetuximab-induced HR and eight with no such history. Cetuximab-specific and galactose-α-1,3-galactose (α-gal) specific IgEs in serum were measured in vitro using an enzyme-linked immunosorbent assay (ELISA). IgE-cetuximab binding on basophils was also analyzed to evaluate the decrease in cetuximab molecules on basophils after dissociation of IgE from FcεRI. The positive predictive value associated with the presence of cetuximab- or α-gal-specific IgE in serum was found to be only 0.67, whereas the negative predictive value was 1.00. On the other hand, in all four patients who developed HR, the cetuximab molecules on basophils were decreased significantly due to the dissociation of IgE from basophils (P < 0.05). However, this was not the case in patients who did not develop HR. In conclusion, our results strongly imply that the IgE-cetuximab interaction on basophils may be key to developing improved methods for predicting severe cetuximab-induced HR.