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

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,I-2 = 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,I-2 = 0%) and in patients using anti-PD-1/PD-L1 (OR 3.22, 95% CI 2.06-5.01,P = 0.00001,I-2 = 32%) monotherapy. The increased odds of irAEs in patients with higher BMI was comparable (test for subgroup differences,P = 0.72,I-2 = 0%) between studies with adjusted OR (OR 2.21, 95% CI 1.44-3.38,P = 0.0003,I-2 = 4%) and unadjusted OR (OR 2.65, 95% CI 1.08-6.50,P = 0.03,I-2 = 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.