Hypersensitivity to therapeutic murine monoclonal antibodies

To determine the predictive value of pre-treatment skin tests and in vitro IgE/IgG4 anti-murine monoclonal antibodies in patients treated with murine monoclonal antibodies.

Patients treated at two cancer institutions were evaluated by skin testing and solid phase immunoassays to detect IgE and IgG4 specific anti-murine monoclonal antibodies. Skin testing by scratch and intradermal skin testing was done on patients before treatment with murine monoclonal antibodies. IgE & IgG4 specific anti-murine monoclonal antibodies were determined before treatment in all patients and at 1, 7, 14 and 21 days post-treatment in 1 patient.

Cancer patients undergoing murine monoclonal antibody treatment in two university medical centers were recruited for the study.

Twelve patients, aged 41-75 years with gastrointestinal cancers (colon, stomach, pancreas or liver) with metastatic disease, who had relapses or conventional therapy were enrolled. Some patients had previous exposure to rodents, either as laboratory personnel or had kept them as pets.

One patient who experienced an anaphylactic reaction to murine monoclonal antibody infusion was desensitized so therapy could continue.

Skin tests, immunoassays, and patient history were correlated with adverse reactions to infusions of murine monoclonal antibodies.

Skin tests (scratch method) and/or in vitro immunoassays may predict allergic outcomes in patients receiving infusions of murine monoclonal antibodies. Intradermal skin testing with murine monoclonal antibodies may result in false positive reactions and have less predictive value. Specific IgE or IgG4 were elevated in the two patients who experienced severe adverse reactions to murine monoclonal antibodies but not in those patients with no reactions and therefore, may have some predictive value. A history of past exposure to mice may also increase the risk of adverse reactions. In one patient, intravenous desensitization enabled treatment to proceed.

Scratch skin tests, in vitro IgE and/or IgG4 immunoassays together with a past history of previous exposure to murine antigen(s) may predict potential allergic reaction to therapy with murine monoclonal antibodies.