Using routine blood tests to predict severe immune-related adverse events during immune checkpoint inhibitor treatment.

backgroundImmune checkpoint inhibitors (ICIs) improve the outcomes across solid tumours, although they can cause severe immune-related adverse events (irAEs). Due to this possibility of side effects, practical and low-cost predictors of severe irAEs are needed to guide patient monitoring and care.

methodsWe conducted a single-centre retrospective cohort study involving 593 patients who were treated with anti-PD-1/PD-L1 monotherapy or anti-PD-1/PD-L1 plus anti-CTLA-4 combination therapy from June 2016 to November 2024. The primary endpoint was the time to the first severe irAE (grade ≥ 3). Peripheral blood biomarkers were evaluated at baseline and immediately before the cycle 3. The cumulative incidence was estimated, and the associations were quantified using the Fine-Gray subdistribution hazards ratio (sHR) model in a competing risks framework.

resultsOverall, 11.6% of patients experienced a severe irAE, with the median time to the first event being 12 weeks and the most frequent severe irAE being colitis (n = 21; 3.5%). Combination therapy was associated with a higher risk when compared with monotherapy (sHR 3.71, 95% confidence interval [CI] 2.25-6.13). Baseline eosinophils > 250/µL were associated with an increased risk (sHR 2.22, 95% CI 1.35-3.65). A lower red cell distribution width (RDW) was likewise associated with the risk at two timepoints: baseline RDW ≤ 15.8% (sHR 2.60, 95% CI 1.35-5.01) and pre-cycle 3 RDW ≤ 14.3% (sHR 2.71, 95% CI 1.44-5.09). The effects were directionally consistent across subgroups, and no interactions were detected. The other blood biomarkers tested were not significant (all p > 0.05).

conclusionsA high baseline eosinophil count and a lower RDW early on during therapy identify patients at increased risk of severe irAEs. These accessible measures could support personalised monitoring and biomarker-guided patient selection. However, external validation is needed to confirm the robustness and validate the thresholds identified in this study prior to clinical use.