C-reactive protein and immune-related adverse events as prognostic biomarkers in immune checkpoint inhibitor treated metastatic renal cell carcinoma patients

Background: There is an ongoing need to identify biomarkers for correct patient selection for immune-oncology treatments in metastatic renal cell carcinoma (mRCC). The aim of our study was to evaluate the prognostic role of elevated C-reactive protein (CRP) values and immune-related adverse events (irAEs) to indicate immune checkpoint inhibitors' (ICIs) efficacy in nivolumab-treated mRCC patients.

Materials and methods: Data from 96 mRCC patients treated with nivolumab at Comprehensive Cancer Center, Helsinki University Hospital in a real-life setting were collected between 2006 and 2020 retrospectively. Patients' baseline CRP, on-treatment (<12 weeks) CRP, and reported irAE association to median survival and outcome were analyzed using Kaplan-Meier and Cox regression.

Results: Patients with elevated baseline CRP were associated with worse overall survival (OS) and progression-free survival (PFS) when compared with normal baseline CRP. This significant correlation was also observed with patients with elevated on-treatment CRP. In multivariate survival analyses both elevated baseline and on-treatment CRP had shorter OS and PFS than patients with normal CRP: hazard ratio (HR) 2.84 (95% CI 1.48-5.42), HR 3.68 (95% CI 1.92-7.03) and PFS: HR 1.77 (95% CI 1.06-2.97), HR 2.88 (95% CI 1.75-4.73), respectively. A significant difference in OS was also seen between patients without irAE and with irAE during treatment. In multivariate survival analyses, patients without irAE had shorter OS HR 1.93 (95% CI 1.03-3.62) compared with patients with reported irAE.

Conclusions: Elevated baseline CRP, on-treatment CRP, and absence of irAE correlate with poor outcome in nivolumb-treated mRCC patients. These results suggest that monitoring CRP values as well as potential irAEs during treatment may be of use in clinical decision making.