Background Our prior study demonstrated that the time-of-day of immune checkpoint inhibitor (ICI) infusion influences clinical outcomes including overall survival (OS) for Stage IV melanoma patients. Similar results have subsequently been shown in lung cancer. In this study, we hypothesized that the time-of-day of ICI infusion may impact OS for patients with stage IV renal cell carcinoma (RCC).

Methods The treatment records of all patients with stage IV RCC who underwent ICI therapy within a multi-center academic hospital system between 2015 and 2020 were reviewed. Association between OS and proportion of ICI infusions received prior to 13:00 (cutoff to denote morning infusions) was evaluated using Cox proportional hazards regression.

Results In this study, there were 201 patients with stage IV RCC (28% female) who were administered ICIs and followed over a median of 18 months (IQR 5–30). Median age at the time of starting ICI treatment was 63 years (IQR 56–70). Initial ICI agents consisted of pembrolizumab (8%), nivolumab (61%), and dual nivolumab/ipilimumab (31%); table 1. The 119 patients (59%) who received at least a quarter of their ICI infusions in the morning had significantly longer OS (median 58 vs. 34 months, HR 0.51, 95% CI 0.29–0.89, P=0.017), independent of age, sex, RCC histology, liver and brain metastases, pre-treatment LDH, and choice of initial ICI; table 2, figure 1.

Conclusions Patients with metastatic RCC may benefit from earlier time-of-day ICI infusions. Our findings are consistent with established mechanisms of chrono-immunology, as well as with preceding analogous studies in melanoma and lung cancer. Additional prospective randomized trials are warranted.

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Abstract 848 Figure 1

Kaplan-Meier overall survival