Prognostic role of plasma levels of γ-glutamyl transpeptidase in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy*

Abstract

Abstract Objective Antibodies targeting programmed cell death protein 1 (PD-1) have become the mainstay of treatment for chemotherapy-refractory gastric cancer, characterized by high levels of programmed cell death ligand-1 (PDL-1) expression. However, the routine clinical implementation of PDL-1 testing is currently limited by the lack of robust detection methods. In this regard, the role of plasma γ-glutamyl transpeptidase (GGT), an N-terminal nucleophilic hydrolase, as an independent predictor of the efficacy of anti-PD-1 therapy remains unknown. In this study, we aimed to assessed the prognostic role of changes in plasma GGT levels (6 weeks vs. baseline) in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy. Methods We retrospectively analyzed data from 57 patients with gastric cancer treated with anti-PD-1 antibodies (camrelizumab, sintilimab, nivolumab, tislelizumab, and toripalimab) at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, from July 2018 to February 2021. Results We found that after 6 weeks of treatment, there were significant differences between responders and non-responders with respect to plasma GGT levels (P < 0.001). Multivariate logistic regression analysis revealed that the continuous value of the 6-week difference in GGT levels (OR = 1.437, 95% CI = 1.116-1.849, P = 0.005) and 6-week difference in GGT ≥ 0 or < 0 (OR = 53.675, 95% CI = 6.379-451.669, P < 0.001) were independent predictors of disease control. Survival analysis indicated that a reduction in plasma GGT6 levels during treatment was significantly associated with a favorable progression-free survival (PFS) and overall survival (P < 0.001). Consistently, univariate and multivariate Cox regression analyses revealed that a reduction in plasma GGT6 levels during treatment was an independent predictor of PFS (HR = 1.033, 95% CI = 1.013-1.053, P = 0.001). Conclusion Alterations in plasma GGT levels during treatment can be used as a predictor of disease progression and survival in patients with advanced gastric cancer undergoing treatment with anti-PD-1 antibodies.