Cancer patients from the Southeastern United States who are treated with the drug cetuximab, known commercially as Erbitux, are far more likely to suffer severe allergic reactions than patients in other regions of the country.
Now researchers from Vanderbilt-Ingram Cancer Center have discovered an underlying clue to this mystery. It appears many of those patients already have a pre-existing antibody that reacts with the cancer drug, causing severe allergic reaction. Christine Chung, M.D., assistant professor of Medicine and Cancer Biology, is the lead author of the study published in the March 13 issue of the New England Journal of Medicine.
Cetuximab is a monoclonal antibody approved for use in colon cancer and squamous-cell head and neck cancer. Chung became curious about the drug when several Vanderbilt-Ingram patients had severe allergic reactions shortly after being infused with the substance. Some of the reactions were life-threatening.
“When I saw my patients having these allergic reactions they looked very much like the anaphylactic reaction in its acuity and symptom presentation as you see with something like severe peanut allergy,” said Chung. “The anaphylactic reactions are triggered by immunoglobulin E or IgE. Patients must be exposed to an antigen before the body becomes sensitized to it and generates IgE. But these cancer patients had never been exposed to the drug cetuximab.
“I thought there must be pre-existing IgE antibodies in these patients from an antigen that is similar to cetuximab,” explained Chung. “While talking to other physicians, we noticed that we were seeing these reactions more frequently in the Southeast.”
Higher rates have been reported in Tennessee, North Carolina, Arkansas, Missouri and Virginia. By contrast, less than 1 percent of patients had such reactions in the Northeast.
Chung joined forces with Vanderbilt-Ingram researchers Jordan Berlin, M.D., Emily Chan, M.D., Ph.D., Barbara Murphy, M.D., and Robbert Slebos, Ph.D. They contacted colleagues at the University of Virginia, Stanford, Duke, Harvard and the Allergy and Asthma Clinic of Northwest Arkansas, along with Bristol-Myers Squibb and ImClone Systems, the drug's manufacturers. The group pooled serum samples from cancer patients, as well as control subjects. Then they tested the samples for the IgE antibody.