Immune checkpoints blockade therapies' efficacy and toxicity in patients with impaired renal function in metastatic bladder cancer.

594Background: In this study, we reported the real-life results of data from impaired renal patients with urothelial carcinoma who were treated with immune checkpoint blockade therapies (ICT). Methods: This study included metastatic urothelial carcinoma patients treated with at least one course of ICT. Impaired renal function was defined as a glomerular filtration rate [GFR] less than 60 mL/min. The patients were categorized into 3 different groups GFR≥60mL/min (normal), 60–30mL/min (low), and less than 30 mL/min (very low) based on GFR. The primary endpoints were the overall response rate (ORR), overall survival (OS), duration of response with ICT, and safety. Median follow-up and OS were estimated using the Kaplan-Meier method. Results: Data from 174 eligible patients were analyzed, 4% of these patients received the ICT as the first line, 83.3 % as the second line, and 12.7 % as the third or more line of treatment. One hundred-five( 60.3%) of patients were GFR normal, 26.4% were GFR low with 30–60 mL/min, and %13.2 were very low group. The median follow-up time was 52 (1.15–62) months. ORR for GFR normal, low, and very low groups were 36% (n=38), 26% (n=12), and %31 (7); p=0.2, respectively. The median duration of response for GFR normal, low, and very low groups were 47.2 months (95% CI, 24.5–51.4), 33.1 months (95% CI, 26.9–47), and 23.5 months (95% CI, 12.2–43.7); p=0.01, respectively. The Median OS rate for GFR normal, low and very low groups were 11.9 (7.2–16.5) months, 4.7 (1.8–7.7), and 6.8 (1.1–13.6) months, p=0.015, respectively. In univariate analysis, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, ECOG PS (1 ≥), and hemoglobin levels < 10 mg/dl were all significantly associated with OS. Three of the adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR=1.6; 95% CI 1.02-3.52; p= 0.043), ECOG PS (1 ≥) HR=2.3; 95% CI 11.05-2.44; p=0.029), and hemoglobin level < 10 mg/dl HR=1.5; 95% CI 1.07-2.34; p: 0.021). In addition, GFR <60 ml/min HR=1.6; 95% CI 1.12-1.80; p=0.02, maintained a significant association with OS in multivariate analysis. GFR normal, low, and very low groups experienced %62.9, 54.3%, and 43.5% of treatment-related adverse events of any grade, respectively. There are no significant differences among each group(p=0.2). Also, treatment-related death and discontinuation were insignificant among each group. Conclusions: Long-term follow-up of real-world data confirms that the overall survival rate and durable response rate with ICT were higher in patients with GFR >60mL/min. On the other hand, we demonstrated that ICT was effective and a long durable response was seen in a group of patients with renal impairment who did not have an effective systemic treatment option, The safety profile was consistent with prior reports and similar in each group.