A protocol for pretreatment testing for antibodies to galactose-alpha-1,3-galactose to mitigate the risk of cetuximab hypersensitivity reactions.

115 Background: Cetuximab has been shown to improve survival in patients with KRAS wildtype metastatic colorectal cancer. However, high rates of hypersensitivity reactions (HSRs) limit its use, with HSR rates up to 10-20%. A major driver of cetuximab HSR is from pre-formed antibody response to galactose-1,3-alpha-galactose (alpha-gal). Evidence from retrospective studies supports alpha-gal pre-screening in this setting. We are the first to report on the impact of prospective alpha-gal antibody screening on cetuximab HSR. Methods: Records were reviewed across three medical oncology centres that have adopted alpha-gal antibody screening measures. Data for patients with metastatic colorectal cancer treated with cetuximab were retrieved. All centres assessed alpha-gal antibody status using the ImmunoCAP ELISA assay. Due to lack of a shared screening approach across study sites, a pre-determined protocol was retrospectively applied to all cases. This protocol allowed cetuximab administration if alpha-gal levels were ≤0.1 kUA/L, but prohibited it if alpha-gal levels were >0.1 kUA/L in favour of panitumumab administration. Patients were allocated to either the Protocol Applied or Protocol Not Applied cohorts based on protocol requirements being met. The primary outcome between these patient groups was the incidence of cetuximab HSRs. Results: Of 254 assessable patients, 39 underwent the pre-treatment screening protocol. Of the Protocol Applied group, 3% (n=1/38) experienced a cetuximab HSR compared to 16% (n=35/215) in the Protocol Not Applied group (Odds ratio (OR) 7.16; 95% CI 1.13–299.61, p =0.02). Patients with alpha-gal antibody titres >0.1 kUA/L were more likely to experience a cetuximab HSR (OR 69.71; 95% CI 5.18–4296.81, p =0.0001). Conclusions: Pre-treatment screening for alpha-gal antibodies significantly reduces the incidence of cetuximab HSRs. A testing threshold of 0.1 kUA/L is effective in identifying patients at risk. Implementing this protocol can improve the safety of cetuximab therapy in high-risk populations.