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.
Keywords: BMI; Cancer immunotherapy; Checkpoint inhibitors; Immune-related adverse events; Obesity; Overweight.