Source: Gastroenterology & Endoscopy News

Hypersensitivity reactions to cetuximab (Erbitux, ImClone Systems/Bristol-Myers Squibb), a monoclonal antibody approved for use in colorectal cancer, are not caused by the drug itself but by preexisting immunoglobulin E (IgE) antibodies that may result from tick bites, researchers have found.

Cetuximab, like other monoclonal antibodies, is generally associated with a low rate of severe anaphylactic reactions (3%), but reports of such reactions to cetuximab have recently increased in southeastern states, including Tennessee and North Carolina. Researchers found IgE antibodies in pretreatment samples of 68% of patients allergic to cetuximab that were specific for galactose-α-1,3-galactose, an oligosaccharide present on the Fab portion of the cetuximab heavy chain.

The authors noted that rates of anaphylactic reaction may be lower with other monoclonal antibodies because cetuximab is produced in the mouse cell line SP2/0, which expresses this oligosaccharide, whereas most other monoclonal antibodies are produced in a Chinese hamster ovary cell line that does not express this molecule.

Theories to explain the increased hypersensitivity of patients in the Southeast initially centered on exposure to worms, such as roundworms or tapeworms. However, researchers now believe the true culprit may be ticks, whose bites have resulted in the development of this type of IgE antibody.

Pretreatment samples were obtained from 76 people treated with cetuximab at centers mainly in Tennessee, Arkansas and North Carolina; the control group included 72 people in Tennessee, 49 patients with cancer in northern California and 341 women in Boston. Of the patients on cetuximab, 25 had an allergic reaction to the drug, and IgE antibodies were found in pretreatment samples from 17 (68%) of them, whereas IgE antibodies were found in the pretreatment sample of only 1 (2%) of the 51 people on cetuximab who did not have an allergic reaction (P<0.001).

The authors believe it may be possible to test patients to determine whether they would be at greater risk for anaphylaxis with cetuximab. The ImmunoCAP assay used in the study to detect IgE antibodies has a sensitivity of 68% and a specificity of 98% for any hypersensitivity reaction; for especially severe reactions, its sensitivity was 92% and its specificity was 90%. However, the assay is in development and not currently available commercially.

—Based on Chung CH et al (N Engl J Med 2008;358:1109-1117)

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

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