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Body mass index and immune-related adverse events in patients on immune checkpoint inhibitor therapies: a systematic review and meta-analysis

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Background

As a result of the growing use of immune checkpoint inhibitors (ICIs) for treating malignancy, immune-related adverse events (irAEs) have been increasingly reported. Higher body mass index (BMI) has been highlighted as a potential risk factor for the development of irAEs. However, there are no meta-analyses summarizing the association between BMI and irAEs in patients on ICI therapies.

Methods

PubMed, MEDLINE, EMBASE, Cochrane and grey literature were searched up to January 2020. Odds ratios (ORs) 95% and confidence intervals (CIs) were summarized using the random-effects model. Heterogeneity test, subgroup and sensitivity analyses were conducted. The protocol was registered on PROSPERO (number registration: CRD42020168790).

Results

Five studies (n = 1937) met eligibility criteria for inclusion. Being overweight or obese was associated with an increased odds of developing irAEs (OR 2.62, 95% CI 1.70–4.03, P ≤ 0.00001, I2 = 53%). In subgroup analyses, higher BMI was associated with irAEs in patients using anti-CTLA-4 single agents or in combination with anti-PD-1/PD-L1 (OR 1.87, 95% CI 1.17–2.98, P = 0.009, I2 = 0%) and in patients using anti-PD-1/PD-L1 (OR 3.22, 95% CI 2.06–5.01, P = 0.00001, I2 = 32%) monotherapy. The increased odds of irAEs in patients with higher BMI was comparable (test for subgroup differences, P = 0.72, I2 = 0%) between studies with adjusted OR (OR 2.21, 95% CI 1.44–3.38, P = 0.0003, I2 = 4%) and unadjusted OR (OR 2.65, 95% CI 1.08–6.50, P = 0.03, I2 = 66%).

Conclusion

Our meta-analysis provides evidence of a relationship between higher BMI (overweight–obesity) and increased risk of irAEs in patients on ICI therapies. Further research is needed to strengthen this association.

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Authors and Affiliations

  1. Clinical Research, International Centre for Medical Research, Dorset, UK

    Yuli Guzman-Prado

  2. Department of Medicine, E. Wolfson Medical Center, Holon, Israel

    Jennifer Ben Shimol

  3. Sackler Faculty of Medicine, Tel Aviv University, Ramat Gan, Israel

    Jennifer Ben Shimol

  4. Alltrista, Christchurch, Dorset, UK

    Ondrej Samson

Authors
  1. Yuli Guzman-Prado
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  2. Jennifer Ben Shimol
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  3. Ondrej Samson
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, analysis and validation were performed by Yuli Guzman-Prado, Jennifer Ben Shimol and Ondrej Samson. The first draft of the manuscript was written by Yuli Guzman-Prado and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yuli Guzman-Prado.

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Yuli Guzman-Prado declares that she has no conflict of interest. Jennifer Ben Shimol declares that she has no conflict of interest. Ondrej Samson declares that he has not conflict of interest.

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Guzman-Prado, Y., Ben Shimol, J. & Samson, O. Body mass index and immune-related adverse events in patients on immune checkpoint inhibitor therapies: a systematic review and meta-analysis. Cancer Immunol Immunother 70, 89–100 (2021). https://doi.org/10.1007/s00262-020-02663-z

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  • DOI: https://doi.org/10.1007/s00262-020-02663-z

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