Abstract
BACKGROUND: Treatment with anti-PD-(L)1 antibodies, approved for several oncology indications, can lead to immune-related adverse events (irAEs). We aimed to investigate risk factors associated with an increased reporting of irAEs in patients treated with PD-(L)1 inhibitors approved for solid tumor indications. PATIENTS AND METHODS: A retrospective review was performed of individual data from patients in phase II/III registrational studies for PD-(L)1 inhibitors in solid tumors. Data on baseline characteristics and adverse events were extracted. Univariate and multivariable logistic regression models were used to identify risk factors. RESULTS: In total, 5123 patients were included from 15 studies reporting on the use of four PD-(L)1 inhibitors for five solid tumor indications. Univariate analysis suggested that type of study drug (P < 0.001), indication (P = 0.003), body mass index (BMI) (P = 0.001), and baseline autoimmune disease (P < 0.001) were associated with an increased occurrence of any irAE. Using logistic regression analyses, three factors were identified as increasing the risk of irAE: BMI ≥ 30 kg/m(2) [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.2-1.8] in comparison to normal BMI, having an autoimmune disease at baseline (OR 1.8, 95% CI 1.1-2.7), and use of a PD-L1 inhibitor (OR 1.6, 95% CI 1.2-2.0). The latter finding is probably biased due to the selection of the studies in the dataset with complete information on baseline characteristics. CONCLUSION: This study was conducted using a large dataset of individual patient data from clinical trials comprising multiple solid tumor indications. We demonstrated that patients with obesity and concurrent autoimmune disease were at increased risk of developing irAEs.