Efficacy and safety of first-line immune checkpoint inhibitor–based combination therapy in metastatic renal cell carcinoma patients on hemodialysis

Background Immune checkpoint inhibitor (ICI)–based combination therapy (ICI plus ICI [IO–IO] or ICI plus tyrosine kinase inhibitor [IO–TKI]) is the standard first-line treatment for metastatic renal cell carcinoma (mRCC), but its impact in patients undergoing maintenance hemodialysis (HD) relative to non-HD patients remains unclear. Methods We retrospectively compared patients with mRCC who received first-line IO–IO or IO–TKI therapy (2018–2025) according to HD status at treatment initiation. Oncologic outcomes (progression-free survival [PFS], overall survival [OS], objective response rate [ORR]) and safety were assessed in the crude cohort and after inverse probability of treatment weighting (IPTW) based on propensity scores. IO–IO and IO–TKI regimens were also compared within the HD cohort. Results Among 601 patients, 37 were receiving HD. In the crude cohort, HD patients had significantly worse PFS, OS, and ORR (37% vs. 57%) than non-HD patients. After IPTW, PFS remained significantly shorter in the HD group (hazard ratios [HR] 1.76, 95% confidence interval [CI] 1.21–2.57; P = 0.003), whereas OS (HR 1.49, 95% CI 0.89–2.50; P = 0.1) and ORR (odds ratios 0.58, 95% CI 0.22–1.54; P = 0.3) were no longer significant. Safety, including Grade ≥3 adverse events, was comparable. Among HD patients, PFS and OS did not differ between IO–IO and IO–TKI regimens. Conclusions In mRCC patients undergoing HD, first-line ICI-based combination therapy was associated with significantly shorter PFS, whereas the worse crude OS and ORR were attenuated after adjustment, largely reflecting baseline prognostic differences rather than reduced efficacy. With a comparable safety profile, it may be a reasonable option in selected patients undergoing HD.