Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study

A novel stratification system based on the positive numbers of independent overall survival (OS) predictors related immune-related adverse events (irAEs) may help guide decision-making for patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab as first-line therapy. Background: Immune checkpoint inhibitors can cause various immune-related adverse events (irAEs). This study aimed to evaluate the association between the incidence of irAEs and oncological outcomes of metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab as first-line therapy. Patients and Methods: We retrospectively analyzed data from 69 patients with mRCC treated with nivolumab plus ipilimumab as first-line therapy between September 2018 and September 2021 at 4 institutions. Cox regression analyses were performed to investigate the important factors affecting overall survival (OS) in patients with mRCC treated with nivolumab plus ipilimumab as firstline therapy. Results: During observation with a median follow-up of 9.1 months, the median OS was not reached, while the median progression-free survival was 6.0 months. Patients with irAEs had significantly prolonged OS and progression-free survival than those without irAEs ( p = .012 and .002, respectively). Multivariate analysis showed that 3 independent factors, including C-reactive protein (CRP), irAEs, and performance status (PS), were significantly associated with OS ( p = .04, .02, and .01, respectively). The patients were subsequently divided into 3 groups as follows: group 1, 20 patients with all 3 independent OS predictors; group 2, 18 patients with irAE predictors alone or 2 positive independent OS predictors (irAEs + CRP or irAEs + PS); group 3, 31 patients with 3 negative independent S predictors. OS varied significantly among the 3 groups ( p = .004). Conclusion: The appearance of irAEs could predict OS in patients with mRCC treated with nivolumab plus ipilimumab as the first-line therapy.