Dataset Information

Distinct patterns of auto-reactive antibodies associated with organ-specific immune-related adverse events.

ABSTRACT: The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined. Here, we analyzed plasma samples longitudinally collected at predefined time points and at the time of irAEs from 58 patients with immunotherapy naïve metastatic non-small cell lung cancer treated on clinical protocol with ipilimumab and nivolumab. We used a proteomic microarray system capable of assaying antibody reactivity for IgG and IgM fractions against 120 antigens for systemically evaluating the correlations between auto-reactive antibodies and certain organ-specific irAEs. We found that distinct patterns of auto-reactive antibodies at baseline were associated with the subsequent development of organ-specific irAEs. Notably, ACHRG IgM was associated with pneumonitis, anti-cytokeratin 19 IgM with dermatitis, and anti-thyroglobulin IgG with hepatitis. These antibodies merit further investigation as potential biomarkers for identifying high-risk populations for irAEs and/or monitoring irAEs during immunotherapy treatment.

Trial registration

ClinicalTrials.gov identifier: NCT03391869.

SUBMITTER: Altan M

PROVIDER: S-EPMC10751952 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Distinct patterns of auto-reactive antibodies associated with organ-specific immune-related adverse events.

Altan Mehmet M Li Quan-Zhen QZ Wang Qi Q Vokes Natalie I NI Sheshadri Ajay A Gao Jianjun J Zhu Chengsong C Tran Hai T HT Gandhi Saumil S Antonoff Mara B MB Swisher Stephen S Wang Jing J Byers Lauren A LA Abdel-Wahab Noha N Franco-Vega Maria C MC Wang Yinghong Y Lee J Jack JJ Zhang Jianjun J Heymach John V JV

Frontiers in immunology 20231212

The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined. Here, we analyzed plasma samples longitudinally collected at predefined time points and at the time of irAEs from 58 patients with immunotherapy naïve metastatic non-small cell lung cancer treated on clinical protocol with ipilimumab and nivolumab. We used a proteomic microarray system capable of assaying antibody reactivity for IgG ...[more]

PMID: 38152395

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Project description:BackgroundAlthough combination therapy with immune checkpoint inhibitors (ICIs) provides a promising efficacy in multiple cancers, their use is facing challenges for a high incidence of adverse effects. This meta-analysis was conducted to compare the risks of organ-specific immune-related adverse events (IRAEs) associated with ICI monotherapy versus combination therapy among cancer patients.MethodsElectronic databases were systematically searched to include eligible randomized controlled trials (RCTs). Any-grade and 3-5 grade IRAEs (colitis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism, and hypophysitis) were extracted for meta-analysis. Two reviewers independently assessed the methodological quality. The RevMan 5.3.5 software was used for meta-analysis.ResultsA total of 10 studies involving 8 RCTs with 2716 patients were included in this study. The most common any-grade adverse event was colitis (14.5%), followed by hypothyroidism (13.8%), hepatitis (10.4%), hypophysitis (10.0%), hyperthyroidism (9.3%), and pneumonitis (4.6%). Meta-analysis showed that ICI combination therapy significantly increased the risks of any-grade IRAEs in colitis [relative risk (RR), 3.56; 95% confidence interval (CI), 1.56-8.12; p < 0.05], pneumonitis (RR, 2.31; 95% CI, 1.54-3.45; p < 0.05), hepatitis (RR, 2.54; 95% CI, 1.65-3.91; p < 0.05), hypothyroidism (RR, 2.17; 95% CI, 1.71-2.76; p < 0.05), hyperthyroidism (RR, 3.13; 95% CI, 2.08-4.70; p < 0.05), and hypophysitis (RR, 3.54; 95% CI, 2.07-6.07; p < 0.05) compared with ICI monotherapy, as well as 3-5 grade IRAEs in colitis (RR, 2.50; 95% CI, 1.62-3.86; p < 0.05), pneumonitis (RR, 1.99; 95% CI, 1.00-3.93; p = 0.05), and hepatitis (RR, 2.70; 95% CI, 1.29-5.63; p < 0.05).ConclusionsThis meta-analysis demonstrated that, compared with ICI monotherapy, patients receiving ICI combination therapy significantly increased organ-specific IRAEs in colitis, hypothyroidism, hepatitis, hypophysitis, hyperthyroidism, and pneumonitis. The incidence and severity of organ-specific IRAEs were drug and dose independent.

Dataset Information

Distinct patterns of auto-reactive antibodies associated with organ-specific immune-related adverse events.

Trial registration

Publications

Distinct patterns of auto-reactive antibodies associated with organ-specific immune-related adverse events.

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