Ipilimumab and Nivolumab in Renal Cell Carcinoma: Real-World Experience in Rare Variant Renal Cell Carcinoma, Brain Metastases and Impact of Immune-Related Adverse Events and Steroid Use

Abstract

Background and Objective

To evaluate the efficacy and toxicity of ipilimumab and nivolumab in advanced clear cell renal cell carcinoma (ccRCC) and rare variant RCC, and assess the impact of immune-related adverse events (irAEs) and steroid use on survival.

Methods

This retrospective study included patients with advanced ccRCC and rare variant RCC treated with first-line ipilimumab and nivolumab at the Royal Marsden Hospital between 2016 and 2025. Survival, toxicity, and the impact of irAEs and steroid use were analyzed using landmark and time-dependent methods.

Key Findings and Limitations

Among 154 patients, 35 had rare variant RCC and 18 had brain metastases (BM). Median follow-up was 20.3 months (ccRCC) and 24.2 months (rare variants). Median overall survival (OS) was 31.9 months (95% CI, 23.5-59.1) for ccRCC and 25.9 months (95% CI, 21.9-not estimable (NE)) for rare variants. Median progression-free survival (PFS) was 9.0 months (95% CI, 7.1-12.8) and 7.2 months (95% CI, 4.6-NE), respectively. Objective response rates (ORR) were 41.0% (ccRCC) and 38.2% (rare variants). In BM patients, median OS was 14.5 months (95% CI, 8.3-NE), PFS 6.2 months (95% CI, 3.3-NE), and ORR 27.8%. Grade 3–4 irAEs occurred in 28.4% and were associated with longer OS at 6-week landmark (NR vs. 23.1 months, P = .033). Prednisone ≥ 40 mg was associated with improved OS (61.2 vs. 22.3 months, P = .021), confirmed on multivariable analysis. Limitations include small sample size and retrospective design.

Conclusions and Clinical Implications

Ipilimumab and nivolumab demonstrated real-world efficacy in both ccRCC and rare variant RCC. Grade 3–4 irAEs and the use of high-dose steroids for their management were associated with improved OS.