Immune checkpoint inhibitors (ICIs) are associated with immune-related (ir) adverse events (AEs) resembling autoimmune diseases. In this retrospective cohort study of patients (pts) treated with ICIs at Oulu University Hospital from 2014–2020, we analysed the spectrum of severe irAEs and their prognostic nature, focusing on rare irAEs. Pts (n = 173) with lung cancer (n = 76, 43.9%), melanoma (n = 56, 32.4%), renal and bladder cancers (n = 34, 19.7%), head and neck cancers (n = 4, 2.3%), SCC (n = 2, 1.2%), and CRC (n = 1, 0.6%) receiving single anti-PD-(L)1 (n = 160) or combination (ICI-ICI n = 9, ICI-chemotherapy n = 4) therapy were included. The survival analysis focused on single anti-PD-(L)1-treated patients with melanoma, lung cancer, and renal and bladder cancers (n = 142). Grade ≥ 3 irAEs of multiple aetiology occurred in 29 patients treated with single-PD-L1 therapy (20.4%), which was associated with improved progression-free survival (PFS) (HR 0.50, CI 0.31–0.78) but not overall survival (OS) (HR 0.88, CI 0.52–1.50). Rare grade ≥ 3 events occurred in 10 (7.0%) pts with no association with PFS (HR 0.90, CI 0.42–1.94). Hence, the presence of rare grade ≥ 3 irAEs was associated with a tendency for inferior OS (HR 1.44, CI 0.66–3.11). Pts with rare grade ≥ 3 irAEs had inferior OS, possibly reflecting the delay in diagnostic workflow and the treatment of irAEs. One explanation for the high incidence of irAEs could be the Finnish population-based genetic variation affecting the immune system.
BackgroundAnti‐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.MethodsWe 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).ResultsIn 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).ConclusionsAdding 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.
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