59 Risk Factors of Immune Related Adverse Events in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

Abstract Background Immune checkpoint inhibitor (ICI) based combinations have become the standard of care for first-line treatment in patients with metastatic renal cell carcinoma (mRCC). However, ICI can be responsible for immune-related adverse events (irAEs). Herein, we aimed to identify risk factors of immune related adverse events (irAEs) in patients treated with current first line (1L) combination of ICIs (ICI+ICI) or ICI with vascular endothelial growth factor (VEGF) targeted therapy (ICI+VEGF). Methods Data was collected retrospectively from patients treated for mRCC at Dana-Farber Cancer Institute, either receiving dual ICI or ICI+VEGF as 1L treatment regimen. Patients were categorized into two groups: those who developed grade ≥ 2 irAEs and those with grade 1 or no AEs. Time to toxicity (TT) was defined as the primary outcome. Univariate Cox regression analysis was initially conducted to identify potential predictive factors associated with irAEs. Subsequently, significant variables related to treatment adverse events were included in a multivariate Cox regression analysis with adjustments for multiple baseline factors. Results Among the 158 patients included, 122 (77.2%) were male, and 36 (22.8%) were female. Median age of patients at the treatment start date of therapy was 61 years (Q1-Q3: 62-69). A total of 57 (36.1%) patients developed grade ≥ 2 irAEs. The median follow-up of patients was 25.7 months. Univariate analysis showed that diabetes, male sex, and ccRCC may indeed influence the development of irAEs with a trend towards significance. However, thrombocytosis could be a protective factor against developing irAEs (p <0.05, Table). Upon multivariate analysis, only ccRCC remained significant as a risk factor for irAEs compared to other subtypes, with a HR of 2.93 (95% CI:1.05-8.18, p = 0.04) (Table). Table: Cox regression analysis for assessment of risk factors associated with irAEs Conclusions In this real-world study, we investigated potential clinical risk factors at baseline related to irAEs in patients with mRCC undergoing ICI-combination therapy. ccRCC histology was significantly associated with a higher risk of developing irAEs compared to other RCC subtypes. The retrospective design and the number of patients could be potential limitations of our findings.