Abstract 218P
Background
Although combination immunotherapies have become a mainstay of treatment for patients with advanced hepatocellular carcinoma (HCC), studies of circulating biomarkers for immunotherapy in HCC are still limited. Therefore, we aimed to evaluate the peripheral T-cell activation phenotype as a biomarker for clinical outcomes of immunotherapies for HCC.
Methods
Baseline blood samples from 86 patients with advanced HCC in three tertiary cancer centers in Korea (ipilimumab-nivolumab [Ipi/Nivo], n=55; nivolumab [Nivo], n=31) were prospectively collected and analyzed.
Results
In the discovery cohort of the Ipi/Nivo group, the peripheral T-cell activation phenotype (IFN-γ+TNF-α+) at baseline was significantly higher in patients with partial response or stable disease compared with those with progressive disease. The cut-off value for high-peripheral T-cell activation phenotype was set to 5.55% using maximally selected rank statistics for optimally predicting survival outcomes. In both the discovery and validation cohorts, the patients with high-peripheral T-cell activation phenotypes showed an increased ORR and more favorable PFS (discovery cohort: hazard ratio [HR], 0.35; 95% CI, 0.16–0.74; P = 0.004; validation cohort: HR, 0.22; 95% CI, 0.04–1.11; P = 0.046) and OS (discovery cohort: HR, 0.44; 95% CI, 0.20–0.99; P = 0.042; validation cohort: HR, 0.20; 95% CI, 0.04–1.02; P = 0.036) than those with low levels. These results were consistent in the Nivo cohort. Regarding immune-related adverse events (irAEs), patients with high-peripheral T-cell activation phenotype showed higher incidence of irAEs compared with those with low levels (14.3% vs. 37.0%). Of note, comparing baseline peripheral blood cytokine levels according to irAEs, the patients with irAEs had significantly lower serum levels of IL-6 at baseline.
Conclusions
Baseline peripheral T-cell activation phenotype was a predictor of clinical outcomes and irAEs in patients with advanced HCC receiving Ipi/Nivo immunotherapy. Patients with lower serum IL-6 levels at baseline might experience more frequent irAEs during Ipi/Nivo treatment in advanced HCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This work was supported by the National Research Foundation of Korea [NRF] grants funded by the Korean government [MSIT] [NRF-2023R1A2C2004339 to HJC, NRF-2023R1A2C2006375 to CK].
Disclosure
C. Kim: Financial Interests, Personal, Advisory Board: Roche, ONO, MSD, BMS, Oncocross, Virocure. H. Chon: Financial Interests, Personal, Advisory Board: Eisai, Roche, Bayer, ONO, MSD, BMS, Celgene, Sanofi, Servier, AstraZeneca, Sillajen, Menarini, GreenCross Cell. All other authors have declared no conflicts of interest.
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