Adjuvant pembrolizumab in clear cell renal cell carcinoma with high recurrence risk: A multicenter real-world study.

e16538 Background: Pembrolizumab has demonstrated efficacy in improving disease-free survival (DFS) and overall survival (OS) as adjuvant therapy in clear cell renal cell carcinoma (ccRCC) at high risk of recurrence. However, real-world evidence supporting its use in Chinese patients remains limited. This study evaluated the real-world effectiveness and safety of adjuvant pembrolizumab in a multicenter cohort. Methods: This multicenter retrospective study recruited 18–80-year-old patients with high-risk clear cell renal cell carcinoma (ccRCC). High-risk status was defined as either M0 disease with adverse pathological features (pT2 with grade 4/sarcomatoid differentiation, any pT3/T4, or any pT with N1) or M1 oligometastatic disease achieving no evidence of disease (NED) after complete resection. The treatment cohort included patients who received at least one cycle of adjuvant pembrolizumab and was 1:2 matched to an observation cohort via propensity score matching to achieve baseline balance. The primary endpoint was DFS; secondary endpoints included OS and treatment-related adverse events (TRAEs). Results: Between January 2023 and December 2025, 396 patients were enrolled, including 114 who received pembrolizumab and 282 managed with observation. Baseline imbalances in age, M stage, and nuclear grade were observed before matching. After matching, 90 patients in the pembrolizumab group and 161 in the observation group were analyzed, with well-balanced baseline characteristics. At the data cutoff (December 31, 2025), median follow-up was 13.1 months in the pembrolizumab group and 24.6 months in the observation group. Disease recurrence occurred in 6.7% (6/90) of patients receiving pembrolizumab compared with 22.4% (36/161) in the observation cohort. Median DFS was not reached in either group (HR 0.56, 95% CI 0.23–1.00). The 24-month DFS rate was 90.5% in the pembrolizumab group versus 73.2% in the observation group. TRAEs were reported in 50.8% of treated patients, predominantly grade 1-2. Grade 3 TRAEs occurred in 13.3% of patients, and grade 4 events were limited to two cases of immune-related myocarditis. The most common TRAEs included rash (21.3%), proteinuria (12.2%) and thyroid dysfunction (10.2%). Severe adverse events (SAEs) led to treatment discontinuation in 10.5% of patients, with hypothyroidism (3.5%), colitis (2.6%) and hypertransaminasemia (2.6%) as the most frequent events, and no treatment-related deaths were noted. Retrospective study design and short follow-up limit long-term outcome assessment. Conclusions: In this multicenter real-world Chinese cohort, adjuvant pembrolizumab was associated with improved DFS and a manageable safety profile in patients with high-risk ccRCC. Larger studies with longer follow-up are warranted to further validate these findings.