# Clinical usefulness of anti-α3Gal immunoglobulin E assays for cetuximab-mediated anaphylaxis in head and neck cancer

## TL;DR

This study compares two tests for detecting anti-α3Gal IgE to predict anaphylaxis risk in patients receiving cetuximab for head and neck cancer.

## Contribution

The study evaluates and compares the clinical utility of two anti-α3Gal IgE assays for predicting cetuximab-induced anaphylaxis.

## Key findings

- Both assays showed 100% sensitivity and negative predictive value for detecting anaphylactic reactions.
- The bTG assay had higher specificity and positive predictive value when using an optimized threshold.
- Anti-α3Gal IgE testing is recommended to safely guide cetuximab use in patients with head and neck cancer.

## Abstract

Fatal anaphylactic reactions to cetuximab remain a clinical issue, although they are associated with preexisting immunoglobulin E (IgE) directed against the galactose-α1,3-galactose epitope (α3Gal). We aimed to compare the clinical usefulness of the two assays and determine the prevalence of preexisting anti-α3Gal IgE.

An anti-α3Gal IgE assay was developed (70BP assay) and compared with a commercial assay [bovine thyroglobulin (bTG) assay]. Both assays were applied to two cohorts: 299 healthy blood donors and 41 patients with head and neck cancer treated with cetuximab, including four patients with a history of anaphylactic reaction (9.8%).

The prevalence of anti-α3Gal IgE was 6% and 5% using 70BP and bTG assays, respectively, in healthy blood donors. Among the head and neck cancer patients, the four who had an anaphylactic reaction were included in the seven (17.1%) and six (14.6%) patients with a signal above the detection threshold using the 70BP and bTG assays, respectively. This resulted in a sensitivity and negative predictive value of 100% for both assays, with a specificity of 91.9% and 94.6%, respectively, and a positive predictive value of 57.1% and 66.6% for the 70BP and bTG assays, respectively. Using an optimized threshold in the bTG assay, the prevalence of anti-α3Gal IgE in blood donors decreased to 1.3%, and five patients (12.2%) were eventually considered positive, giving a specificity of 97.3% and a positive predictive value of 80%.

The predictive value of anti-α3Gal IgE using these two assays was excellent and useful in clinical practice.

•Use of cetuximab combined with radiotherapy or chemotherapy were standard of care in head and neck cancer.•Hypersensitivity reactions to cetuximab could be fatal due to anaphylactic reactions.•Measurement of anti-alpha-Gal IgE levels before prescribing cetuximab is recommended to predict infusion reaction risks.•In case of negative results (<0.1 kAU/l level using bTG assay), cetuximab can be safely used in patients with head and neck cancer.•In case of positive results (>0.1 kAU/l level using bTG assay), more data are needed to ensure the safe use of cetuximab.

Use of cetuximab combined with radiotherapy or chemotherapy were standard of care in head and neck cancer.

Hypersensitivity reactions to cetuximab could be fatal due to anaphylactic reactions.

Measurement of anti-alpha-Gal IgE levels before prescribing cetuximab is recommended to predict infusion reaction risks.

In case of negative results (<0.1 kAU/l level using bTG assay), cetuximab can be safely used in patients with head and neck cancer.

In case of positive results (>0.1 kAU/l level using bTG assay), more data are needed to ensure the safe use of cetuximab.