Early Change in C-Reactive Protein and Venous Thromboembolism in Patients Treated With Immune Checkpoint Inhibitors

Patients with cancer treated with immune-checkpoint inhibitors (ICIs) have a substantial risk of venous thromboembolism (VTE). The association between ICI-induced inflammation and hypercoagulability is unclear, and no biomarkers currently exist to stratify VTE risk.

The authors sought to determine the association between the early changes in C-reactive protein (CRP) after ICI initiation and the risk of VTE.

This retrospective cohort study included patients with cancer initiating ICI therapy from 2 academic cancer centers, serving as discovery and external validation cohorts. Patients were stratified based on CRP trajectories during the first 3 months of ICI treatment, with a CRP rise defined as a 2-fold increase from baseline. Patients were followed for VTE for the duration of ICI therapy, and competing risk and time-dependent analyses were used.

A total of 822 patients were included. In the discovery cohort (n = 405), the cumulative VTE incidence in patients with a CRP rise (n = 159, 39.3%) was 19.9% (95% CI: 8.4%-34.8%), compared with 8.6% (3.1%-17.6%) in those without a CRP rise. After adjusting for key patient- and cancer-specific confounders, the subdistribution HR for VTE in patients with a CRP rise was 2.64 (95% CI: 1.06-6.62). This was confirmed in the external validation cohort (n = 417; subdistribution HR: 2.25; 95% CI: 1.03-4.94), with VTE incidences of 22.9% (95% CI: 9.7%-39.3%) in patients with a CRP rise and 10.8% (95% CI: 7.4%-15.1%) in those without. The association between CRP rise and VTE risk was confirmed in a time-dependent analysis and was consistent after adjusting for disease progression as a potential time-dependent confounder.

Early CRP changes during ICI therapy are associated with an increased risk of VTE, suggesting a potential association between ICI-induced inflammation and hypercoagulability. CRP trajectories may serve as a biomarker for ICI-associated VTE.