Validation of an anti-α-Gal IgE fluoroenzyme-immunoassay for the screening of patients at risk of severe anaphylaxis to cetuximab

Background The link between immediate hypersensitivity reactions (HSR) following the first cetuximab infusion and the IgE sensitization against anti-galactose-alpha-1,3-galactose (alpha-Gal) is now well-established. An automated Fluoroenzyme-Immunoassay (FEIA) is available and may facilitate the screening of patients with anti-alpha-Gal IgE before treatment. Methods This study aimed to evaluate its performances as compared to a previously validated anti-cetuximab IgE ELISA, using 185 samples from two previously studied cohorts. Results Despite 21.1% of discrepancies between the two techniques, FEIA discriminated better positive patients and similarly negative ones with a >= 0.525 kU(A)/L threshold. Sensitivity was 87.5% for both tests, specificity was better for FEIA (96.3% vs ELISA: 82.1%). FEIA had a higher positive likelihood ratio (23.9 vs ELISA: 4.89) and a similar negative likelihood ratio (0.13 vs ELISA: 0.15). In our population, the risk of severe HSR following a positive test was higher with FEIA (56.7% vs ELISA: 19.6%) and similar following a negative test (0.7% vs ELISA: 0.8%). Conclusion Although the predictive value of the IgE screening before cetuximab infusion remains discussed, this automated commercial test can identify high-risk patients and is suitable for routine use in laboratories. It could help avoiding cetuximab-induced HSR by a systematic anti-alpha-Gal IgE screening before treatment.

Automated summary

This study compared the performances of an automated Fluoroenzyme-Immunoassay (FEIA) for screening anti-alpha-Gal IgE with a previously validated anti-cetuximab IgE ELISA. The results showed that FEIA had better discrimination of positive and negative patients, higher specificity, and a higher positive likelihood ratio compared to ELISA. The risk of severe HSR following a positive test was higher with FEIA, while the risk following a negative test was similar.