High body mass index and pre-existing autoimmune disease are associated with an increased risk of immune-related adverse events in cancer patients treated with PD-(L)1 inhibitors across different solid tumors

Abstract

Available online xxxBackground: Treatment with anti-PD-(L)1 antibodies, approved for several oncology indications, can lead to immunerelated 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 ¼ 0.003), body mass index (BMI) (P ¼ 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.

Association of Body Mass Index With the Safety Profile of Nivolumab With or Without Ipilimumab

“…[3][4][5][6][7][8][9][10][11] Studies on the BMI-safety association using clinical trial data have shown heterogeneous results, with some studies indicating no association 7 and others suggesting an increased risk. 20,22 Similarly, meta-analyses 12,21 have demonstrated heterogeneous results. Our study analyzed primary trial data in which irAEs were uniformly defined across the trials and included 2746 patients receiving nivolumab monotherapy and 1026 patients treated with combination therapy.…”

“…Obesity, a risk factor for developing many tumor types, has paradoxically been associated with improved outcomes for patients receiving ICIs . Studies on the BMI-safety association using clinical trial data have shown heterogeneous results, with some studies indicating no association and others suggesting an increased risk . Similarly, meta-analyses have demonstrated heterogeneous results.…”

“…Nivolumab dose is calculated with actual BW, 13 whereas some oncologists calculate cytotoxic chemotherapy dosing with adjusted BW or body surface area. 19 Retrospective analyses investigating the association between BMI and risk of immune-related adverse events (irAEs) have been heterogeneous, with some showing higher incidence among patients with overweight or obesity vs normal BMI, [20][21][22] whereas others have found no significant association between BMI and incidence of irAEs. 7,12 This analysis builds on previous studies to further investigate the potential association between BMI and safety among patients receiving ICIs by using existing randomized clinical trial data with rigorous, prospectively collected AE grading and reporting.…”

The safety concerns regarding immune checkpoint inhibitors in liver cancer patients rising mainly from CHB

“…Previous studies have shown that a higher BMI increases the risk of irAEs in patients with NSCLC, melanoma, renal cell carcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, suggesting that BMI may contribute to irAEs ( Cortellini et al, 2020 ; Gülave et al, 2021 ; Leiter et al, 2021 ). In our study of patients with primary liver cancer, we observed that patients with irAEs had a higher BMI compared to non-irAE patients, with overweight patients experiencing an increased incidence of irAEs.…”

Peripheral absolute eosinophil count identifies the risk of serious immune-related adverse events in non-small cell lung cancer

“…In a study of solid tumors, high serum albumin levels were discovered to be a risk factor for irAEs (24). Another retrospective analysis in the field of pan-cancer found that patients with high BMI had a higher probability of experiencing irAEs (25). Patients who experienced severe immune-related pneumonitis had a significant morbidity and mortality rate, according to a retrospective investigation by Suresh et al in NSCLC, but no additional research into predictors was done (26).…”