The role of IgE specific for galactose-α-1,3-galactose in predicting cetuximab induced hypersensitivity reaction: a systematic review and a diagnostic meta-analysis

Lungulescu, Cristian Virgil; Ungureanu, Bogdan Silviu; Turcu-Știolică, Adina; Ghimpau, Valentina; Artene, Stefan Alexandru; Cazacu, Irina M.; Grecu, Alexandru Florian; Dinescu, Venera Cristina; Croitoru, Adina

doi:10.1038/s41598-020-78497-7

Cited by 12 publications

(5 citation statements)

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“…According to Lungulescu et al, a total of six studies assessed the diagnostic accuracy of the anti-IgE for galactose-α-1,3-galactose in patients with HSRs to Cetuximab. The meta-analysis concluded that more studies are needed to establish a protocol necessary for the proper prediction and avoidance of HSR related to Cetuximab [32]. Hence, we consider that the theme of the paper is important and interesting, even though it might seem to be without great novelty.…”

Section: Discussionmentioning

confidence: 96%

“…A classic mAbs adverse effect is the triggering of hypersensitivity reactions (HSR), which most commonly can occur with the first infusion. Numerous studies highlight the triggering of hypersensitivity reactions as being related to the pre-existence of specific IgE antibodies [32][33][34]. It is already known that some people are more likely to develop IgE antibodies against galactose-α-1,3-galactose after being naturally exposed to galactose-α-1,3-galactose.…”

Section: Discussionmentioning

confidence: 99%

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A Preliminary Study Examining the Correlation between EGFRI Treatment, Clinic Dermatoscopy Features, and Serum Levels of Anti-Alpha-Galactosyl IgE in Colorectal Cancer Patients

Popa,

Cherciu Harbiyeli,

Ciurea

et al. 2024

Gastroenterology Insights

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The introduction of molecularly targeted therapies, particularly the epidermal growth factor receptor inhibitors (EGFRIs), has had a positive impact by increasing the life expectancy of patients with advanced colorectal cancer (CRC). The most used anti-EGFRIs monoclonal antagonist, Cetuximab, induces skin responses in most patients, leading to a reduction of dosages or even therapy discontinuation, all with devastating effects. Our study aimed to assess the predictive role and the possible correlations of clinical features, imaging aspects (dermatoscopy), and laboratory tests (anti-alpha-galactosyl IgE levels) for early detection of Cetuximab skin toxicity in patients with metastatic CRC. The association of IgE antibodies against goat alpha-1,3-galactose serum levels with various degrees of skin toxicity encountered during the oncologic treatment resulted in higher concentrations in patients with pruritus and hair changes. Incorporating dermatoscopy into the routine dermatological consultation allowed us to perform a severity assessment, dynamically record, and identify even the erupting lesions previously invisible to classical examination. Hence, we were enabled to generate a broad report and to classify various degrees of skin toxicity severity linked to Cetuximab treatment in 19 patients with metastatic CRC. Detecting the emergent lesions and initiating dermatological treatment in the early stages decreased the severity of skin toxicity. As a result, the duration of the antibiotic treatment was much shorter, and the risk of dose reduction or interruption of the cancer treatment was diminished. In conclusion, we emphasize the need for a regular dermatological examination with dermatoscopy of CRC patients undergoing Cetuximab treatment. Skin toxicity is a significant concern for these patients, and healthcare providers should be vigilant in monitoring and managing this side effect in order to optimize patient care. The correlation between anti-alpha-Gal IgE levels and Cetuximab-induced skin toxicities is an emerging area. More extensive studies need to be published in order to establish this relationship directly.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

A Preliminary Study Examining the Correlation between EGFRI Treatment, Clinic Dermatoscopy Features, and Serum Levels of Anti-Alpha-Galactosyl IgE in Colorectal Cancer Patients

Popa,

Cherciu Harbiyeli,

Ciurea

et al. 2024

Gastroenterology Insights

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“…These results are in line with a meta-analysis performed to assess the diagnosis accuracy of anti-α-Gal IgE in predicting the risk of cetuximab immediate HSR. From a compilation of 6 studies, the authors reported a pooled sensitivity of 73% (95% CI 62–81%) and a pooled specificity of 88% (95% CI 79–94%) [ 13 ]. Two studies included in this meta-analysis used ImmunoCap o215.…”

Section: Discussionmentioning

confidence: 99%

“…In sensitized patients, immediate HSR can occur following the first cetuximab infusion, highlighting the importance of identifying high risk patients [ 11 , 12 ]. Thus, an anti-cetuximab IgE screening has been suggested as a reliable strategy to identify those patients [ 13 ]. Moreover, we have validated an ELISA method in a prospective multicenter study for the screening of patients at high risk of immediate HSR before cetuximab infusion [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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Background The link between immediate hypersensitivity reactions (HSR) following the first cetuximab infusion and the IgE sensitization against anti-galactose-α-1,3-galactose (α-Gal) is now well-established. An automated Fluoroenzyme-Immunoassay (FEIA) is available and may facilitate the screening of patients with anti-α-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 kUA/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-α-Gal IgE screening before treatment.

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“…However, meta-analyses have shown an increased risk of acute infusion reactions with antibodies to infliximab [35,36]. With regard to other specific IgE-testing, anti-Galactose-α-1,3-galactose (alphagal) IgE testing may be helpful in predicting the risk of immediate reaction with first administration of cetuximab, demonstrating a pooled sensitivity of 73% (95% CI 62-81%) and specificity of 88% (95% CI 79-94%) in a recent metaanalysis [18,37,38]. The alpha-gal epitope has also been demonstrated on abatacept and infliximab; reactions to abatacept and infliximab have been reported in patients with alpha-gal syndrome, although evidence is limited to whether these were directly due to alpha-gal.…”

Section: In Vitro Testsmentioning

confidence: 99%

Adverse Reactions to Biologic Medications Used in Allergy and Immunology Diseases

Chow

Franzblau

Khan

2022

Curr Allergy Asthma Rep

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Purpose of ReviewThe use of biologic therapies has risen exponentially over recent years, allowing for unprecedented disease control within numerous areas of Allergy/Immunology. With this expanded use, awareness and understanding of adverse reactions to biologic agents have also increased. Recent Findings Multiple biologic adverse reaction phenotypes have been described, but significant overlap in clinical features across phenotypes exists. Given considerable phenotypic overlap, a targeted testing approach may not always be clear, and more recent classifications focus on management decision making using tools of diagnostic challenges and rapid drug desensitizations, guiding clinicians in developing a management plan when the exact underlying mechanism is not clearly known. With increased clinical experience with omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab, rituximab, and TNF-inhibitors, there is a growing appreciation to the spectrum and particularities of adverse reactions to these agents which are outlined in this review. Summary Our understanding of the clinical presentation and management of adverse reactions to biologic medications encountered in Allergy/Immunology has grown. Opportunities remain to further define optimal diagnostic and management strategies for these reactions.

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The role of IgE specific for galactose-α-1,3-galactose in predicting cetuximab induced hypersensitivity reaction: a systematic review and a diagnostic meta-analysis

Cited by 12 publications

References 44 publications

A Preliminary Study Examining the Correlation between EGFRI Treatment, Clinic Dermatoscopy Features, and Serum Levels of Anti-Alpha-Galactosyl IgE in Colorectal Cancer Patients

A Preliminary Study Examining the Correlation between EGFRI Treatment, Clinic Dermatoscopy Features, and Serum Levels of Anti-Alpha-Galactosyl IgE in Colorectal Cancer Patients

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

Adverse Reactions to Biologic Medications Used in Allergy and Immunology Diseases

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