Adverse events after nivolumab and ipilimumab combined immunotherapy in advanced renal cell carcinoma: a multicentre experience in Poland

Background: Immune checkpoint inhibitors (ICIs) have been employed in the adjuvant and metastatic setting of renal cell carcinoma (RCC) treatment. Among ICIs, combined immunotherapy has the highest risk for immune-related adverse events (irAEs). We aimed to document the incidence of irAEs in RCC patients treated with nivolumab and ipilimumab (O+Y), as data from the European population remain limited. Materials and methods: We analysed data from 88 RCC patients treated with O+Y between May 2022 and June 2024 across six high-volume oncology units in Poland. We reviewed irAEs and estimated their impact on survival parameters via univariate and multivariate Cox proportional hazards regression models, along with log-rank tests. Results: With a median follow-up of 11.3 months, the median overall survival (OS) was not reached, whereasthe median progression-free survival (PFS) was 12.8 months (6.3–19.3). A total of 74 irAEs were recorded in 50 patients. The most frequent events were endocrine (n=20, 27%), hepatic (n=15, 17%), general (n=12, 13.6%), and cutaneous (n=11, 12.5%). The occurrence of irAEs was associated with a 60% lower risk of disease progression (hazard ratio 0.44, 95% confidence interval 0.2–0.87, p=0.018) without impacting OS and higher disease control rate (n=45, 90% vs. n=24, 63.2%, p=0.004). In contrast, patients with hepatotoxicity had poorer outcomes, with a 2.6-fold greaterrisk of death (p=0.05). Conclusions: IrAEs may serve as a predictive factor for the efficacy of the O+Y regimen in RCC patients. Special attention is needed for hepatotoxicity, as it can significantly impact survival outcomes.