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A protocol for pre-treatment testing for antibodies to galactose-alpha-1,3-galactose to mitigate the risk of cetuximab hypersensitivity reactions – a retrospective cohort review

Year: 2025

Type: article

Abstract: PURPOSE: Cetuximab improves survival in 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 IgE antibody response to galactose-1,3-alpha-galactose (alpha-gal). Evidence from retrospective studies supports alpha-gal pre-screening in this setting. This study reports the impact of prospective alpha-gal antibody screening on cetuximab HSR. PATIENTS AND 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 levels using the ImmunoCAP® immunoassay. Due to variability in alpha-gal screening practices across study sites, a standardised protocol was applied to all cases. This protocol allowed cetuximab administration if alpha-gal levels were ≤0.10 kUA/L, but prohibited it if alpha-gal levels were >0.10 kUA/L in favour of panitumumab administration. Patients were allocated to either the Alpha-gal Pre-screening Applied ('Pre-screening') or Alpha-gal Pre-screening Not Applied ('Reference') 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 Pre-screening group, 3% (n=1/39) experienced a cetuximab HSR compared to 16% (n=35/215) in the Reference group (Odds ratio (OR) 0.14; 95% CI 0.0033-0.86, p= 0.02). Patients with alpha-gal antibody titres >0.10 kUA/L were more likely to experience a cetuximab HSR (OR 69.71; 95% CI 5.18-4296.81, p=0.0001). CONCLUSION: Pre-treatment screening for alpha-gal antibodies significantly reduces the incidence of cetuximab HSRs. A testing threshold of 0.10 kUA/L is effective in identifying patients at risk. Implementing this protocol can improve the safety of cetuximab therapy in high-risk populations. MICRO ABSTRACT: Hypersensitivity reactions (HSRs) limit cetuximab use in KRAS wildtype advanced colorectal cancer, with a significant driver being pre-formed IgE antibodies against galactose-1,3-alpha-galactose (alpha-gal). Our multicentric retrospective study assessed the impact of prospective alpha-gal antibody screening on HSR incidence following cetuximab administration. Of 254 assessable patients, pre-treatment alpha-gal antibody screening significantly reduced the incidence of cetuximab HSRs (3% vs 16%; OR 0.14, p=0.02). Our findings support pre-treatment alpha-gal screening to improve safety of cetuximab therapy in high-risk populations.

Source: Cancer Treatment and Research Communications

DOI: 10.1016/j.ctarc.2025.100969