Work

971 The impact of liver metastases on immune-related adverse events in stage IV patients treated with immune-checkpoint inhibitors: a real-world, multicenter, retrospective study

Year: 2026

Type: conference-abstract

Abstract: Background Immune-related adverse events (irAEs) reflect systemic immune activation during immune checkpoint inhibitor (ICI) therapy 1 and have been associated with improved clinical outcomes across several malignancies.2–4 In contrast, liver metastases have been linked to systemic immune suppression and reduced responsiveness to ICIs.5 We evaluated whether liver metastases were associated with differences in irAE development and survival outcomes in metastatic cancer patients treated with ICIs.Methods Patients treated with ICIs were identified from a multi-institutional immuno-oncology registry. The analytic cohort included metastatic patients with and without liver involvement and available treatment and survival data. Logistic regression models adjusted for age, sex, race, and cancer type were used to evaluate associations between liver metastases and irAE development. Overall survival (OS) was assessed using Kaplan-Meier curves and multivariable Cox proportional hazards models adjusted for age, sex, race, ECOG performance status, and immunotherapy regimen. Baseline covariate adjustment in survival analysis models used inverse probability of treatment weighting (IPTW). A 12-week landmark sensitivity analysis excluded patients who developed their first irAE after 12 weeks and patients without irAEs who received <6 weeks of ICI exposure.Results The final metastatic cohort included 708 patients, including 148 patients with liver metastases and 560 without liver involvement. Patients with liver metastases demonstrated lower rates of any irAE compared with patients without liver metastases (32% vs. 48%, p < 0.001). In multivariable logistic regression analyses, liver metastases were associated with significantly lower odds of any irAE development (OR 0.50, 95% CI 0.33–0.74) and grade 1–2 irAEs (OR 0.49, 95% CI 0.30–0.77), but not grade ≥3 irAEs (OR 1.36, 95% CI 0.64–2.81). Among patients with liver metastases, irAE development was associated with improved OS in adjusted Cox models (HR 0.59, 95% CI 0.38–0.93, p = 0.022). This association persisted in IPTW-adjusted analyses (HR 0.54, 95% CI 0.44–0.66, p < 0.001). In the 12-week landmark sensitivity analysis, the association between early irAE development and OS was attenuated and no longer statistically significant (HR 0.82, 95% CI 0.65–1.04, p = 0.106).Conclusions Liver metastases were associated with reduced irAE development in metastatic patients treated with ICIs, supporting the hypothesis that hepatic metastases contribute to systemic immune suppression. Although irAE development was associated with improved survival in primary and IPTW-adjusted analyses, attenuation in landmark analyses suggests that part of this association may reflect time-dependent bias. These findings support the biologic relevance of irAEs while highlighting the importance of temporally robust sensitivity analyses in immuno-oncology outcomes research.References Ramos-Casals M, Brahmer JR, Callahan MK, et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers. 2020;6:38.Foster CC, Couey MA, Kochanny SE, et al. Immune-related adverse events are associated with improved response, progression-free survival, and overall survival for patients with head and neck cancer receiving immune checkpoint inhibitors. Cancer 2021;127:4565-4573.Cook S, Samuel V, Meyers DE, et al. Immune-related adverse events and survival among patients with metastatic NSCLC treated with immune checkpoint inhibitors. JAMA Netw Open. 2024;7:e2352302.Ricciuti B, Naqash AR, Naidoo J, et al. Association between immune-related adverse events and clinical outcomes to programmed cell death protein 1/programmed death-ligand 1 blockade in SCLC. JTO Clin Res Rep. 2020;1:100074.Chen XJ, Ren A, Zheng L, et al. Pan-cancer analysis identifies liver metastases as negative predictive factor for immune checkpoint inhibitors treatment outcome. Front Immunol. 2021;12:651086.Ethics Approval This study used data from an institutional immuno-oncology registry approved by the Georgetown University Institutional Review Board (IRB #2017-0559). Informed consent was waived.

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-sitc2026.0971