LIFE-THREATENING CETUXIMAB ANAPHYLAXIS: CAUTIONARY TALES & POSSIBLE IGE CONSUMPTION DURING A DRUG-INDUCED ANAPHYLAXIS

LIFE-THREATENING CETUXIMAB ANAPHYLAXIS: CAUTIONARY TALES & POSSIBLE IGE CONSUMPTION DURING A DRUG-INDUCED ANAPHYLAXIS

 Susannah Lauer1,2, Alex Yuile3, Connie Diakos4,5, Stephen Clarke3,4,5, Nick Pavlakis.3,4,5, Sheryl van Nunen2,3,5

 1 Gold Coast University Hospital, Southport, Australia , ²Tick-induced Allergies Research and Awareness Centre, Sydney, Australia, 3 Royal North Shore Hospital,  Sydney, Australia, 4 Northern Cancer Institute, Sydney, Australia, 5 The University of Sydney, Sydney, Australia

Background:  Cetuximab, an anti-EGFR mouse-human chimeric monoclonal antibody, contains lower-order mammalian antigen, galactose-alpha-1,3-galactose (alpha-gal).  It is used in treatment of advanced colorectal (ACRC) and head and neck cancers.  Sensitization to alpha-gal occurs in humans after tick bites.  Lethal anaphylaxis has occurred to cetuximab, typically with the first dose.  In tick-hyperendemic regions world-wide, 35% of the population are sensitized to alpha-gal, however, <10% have a history of cross-reactive mammalian meat allergy (MMA).  A preliminary study of screening for alpha-gal specific-IgE has shown efficacy in preventing cetuximab anaphylaxis. Establishing the mechanism of these reactions underpins subsequent clinical decisions.  IgE consumption is not believed to occur in drug-induced anaphylaxis. 

Methods: Two case reports are presented. Both ACRC (RAS wildtype) patients suffered profound anaphylaxis (Grade 3 Brown classification) with first dose cetuximab.

Results:  Both patients resided in tick-hyperendemic areas of northern Sydney

Conclusions:  Very low levels of alpha-gal sIgE can translate to life-threatening anaphylaxis when allergen is administered intravenously as cetuximab. Negative alpha-gal ImmunoCAP® results on the day of the reaction (Patient 1) do not appear to be due to haemodilution or test variability, with consumption of IgE during anaphylaxis a possible explanation.  Screening for alpha-gal sensitization is the safest approach in tick hyperendemic regions, as bites from nymph stage ticks are often not recognized as tick bites. Panitumumab skin testing was negative. 

Melanie Burk