Unusually high rates of hypersensitivity to cetuximab in the middle-southern United States: Association with atopic phenotype

Abstract

9051 Purpose: To confirm the anecdotal observation that pts in North Carolina (NC) and Tennessee (TN) treated with cetuximab (C-mab) experience hypersensitivity reactions (HSR) at a much higher rate than that reported nationally and internationally (= 3%). Methods: Data from pts treated with C-mab on clinical trials (CTs, n = 88) at 3 research sites in TN and NC were analyzed for grade 3 or 4 HSR. Additional information was obtained from medical records under IRB approval at the University of North Carolina (UNC) for 90 pts (including 35 pts on CTs) to determine whether history of other significant allergy was a risk factor for HSR. Prior allergy was defined as history of H1 antagonist use, or notation in the medical record of significant drug allergy (excluding narcotic allergies), bee sting allergy, eczema, allergic reactive airways disease, or food allergy. Pearson's or Fisher's exact tests were used for comparison of proportions. Results: Data for 88 pts on CTs and an additional 55 pts treated outside of CTs was included in this analysis. Pts had a variety of tumor types, the most frequent being colorectal and lung For the CT group (n = 88), the overall rate of grade 3 to 4 HSR was 21.6%, significantly higher than the rate noted in any large published trial (p < 0.0001 for comparison to data from Cunningham et al). All HSRs occurred during the first dose. There was no apparent protection from HSR afforded by premedication with dexamethasone in either the CT cohort or the overall UNC cohort. Upon examination of medical records of 90 pts treated at UNC (14.4% gr 3/4 HSR overall), there was a strong relationship between prior allergy history and chance of HSR; 10/28 pts with any HSR vs. 7/62 without allergy history (p = 0.006), and grade 3/4 HSR occurred in 8/28 versus 5/62, respectively (p = 0.01). Conclusions: At the sites in neighboring Southern US states studied, HSR was far more common than reported in national studies. History of prior allergy is a strong predictor of HSR, although is not specific enough to be used as the sole means of excluding pts from therapy. Further investigation of more specific predictors of HSR in the US Middle South is warranted, and pts being treated with C-mab in the region should be observed particularly closely during their first infusion. No significant financial relationships to disclose.