The prognostic and predictive roles of plasma C-reactive protein and PD-L1 in non-small cell lung cancer

Abstract

Background: Anti-PD-(L)1 agents have revolutionized the treatment paradigms of non-small cell lung cancer (NSCLC), while predictive biomarkers are limited. It has been previously shown that systemic inflammation, indicated by elevated C-reactive protein (CRP) level, is associated with a poor prognosis in anti-PD-(L)1 treated. The aim of the study was to analyze the prognostic and predictive value of CRP in addition to traditional prognostic and predictive markers and tumor PD-L1 score.

Methods: We identified all NSCLC patients (n = 329) who had undergone PD-L1 tumor proportion score (TPS) analysis at Oulu University Hospital 2015-22. CRP levels, treatment history, immune checkpoint inhibitor (ICI) therapy details, and survival were collected. The patients were categorized based on CRP levels (≤10 vs. >10) and PD-L1 TPS scores (<50 vs. ≥50).

Results: In the whole cohort (n = 329), CRP level of ≤10 mg/L was associated with improved survival in univariate (HR 0.30, Cl 95% 0.22-0.41) and multivariate analyzes (HR 0.44, CI 95% 0.28-0.68). With ICI treated (n = 70), both CRP of ≤10 and PD-L1 TPS of ≥50 were associated with improved progression-free survival (PFS) in univariate (HR 0.51, CI 95% 0.27-0.96; HR 0.54, CI 95% 0.28-1.02) and multivariate (HR 0.48, CI 95% 0.26-0.90; HR 0.50, CI 95% 0.26-0.95) analyzes. The combination (PD-L1 TPS ≥50 and CRP >10) carried a high negative predictive value with a median PFS of 4.11 months (CI 95% 0.00-9.63), which was similar to patients with low PD-L1 (4.11 months, CI 95% 2.61-5.60).

Conclusions: Adding plasma CRP levels to PD-L1 TPS significantly increased the predictive value of sole PD-L1. Furthermore, patients with high CRP beard little benefit from anti-PD-(L)1 therapies independent of PD-L1 score. The study highlights the combined evaluation of plasma CRP and PD-L1 TPS as a negative predictive marker for ICI therapies.

Keywords: CRP; ICI; NSCLC; PD-L1; predictive; prognostic.

FIGURE 1

Kaplan–Meier analysis for overall survival according to (A) peripheral blood C‐reactive protein (CRP) level (B) Programmed death‐1 receptor (PD‐1) and its ligand (PD‐L1) tumor proportion score (TPS) score in the whole study population. Crosses indicate censored events.

FIGURE 2

Kaplan–Meier analysis for progression‐free survival according to (A) peripheral blood C‐reactive protein (CRP) level, (B) Programmed death‐1 receptor (PD‐1) and its ligand (PD‐L1) tumor proportion score (TPS) score, (C) PD‐L1 TPS score in patients with peripheral blood CRP ≤ 10, and (D) PD‐L1 TPS score in patients with peripheral blood CRP > 10, (E) PD‐L1 TPS divided in the three categories in patients with CRP ≤10, (F) PD‐L1 TPS divided in the three categories in patients with CRP > 10. Crosses indicate censored events.