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γ-Glutamyltransferase is reportedly associated with survival in local and metastatic renal cell carcinoma patients; however, its predictive role among patients treated with immune-checkpoint inhibitors are unknown. This study aimed to investigate the role of γ-glutamyltransferase as a predictive marker among metastatic renal cell carcinoma patients undergoing nivolumab therapy. We retrospectively evaluated 69 nivolumab-treated metastatic renal cell carcinoma patients upon failure of one or more systematic therapies. Serum γ-glutamyltransferase levels were determined at baseline and 2 months after nivolumab treatment initiation. Patients were classified as high (≥ 49 U/L) and low (< 49 mg/dL) from baseline GGT levels and the outcomes were compared between the two groups. Furthermore, increased (after/baseline ≥ 2) and non-increased (after/baseline < 2) groups were compared. Progression-free survival and overall survival were evaluated after nivolumab initiation. Overall survival was significantly shorter in the high baseline γ-glutamyltransferase group (20.3%) than in the low group (79.7%) (median 2.33 vs not reached [months], p = 0.0051). Progression-free survival and the overall survival were significantly shorter in the increased than in the non-increased group (24.6% and 75.4%, respectively) (median PFS: 4.43 vs 7.23 [months], p = 0.0373/OS: 24.00 vs not reached, p = 0.0467). On multivariate analyses, high baseline γ-glutamyltransferase was an independent factor for overall survival (p = 0.0345) and increased γ-glutamyltransferase was an independent factor for progression-free survival (p = 0.0276) and overall survival (p = 0.0160). High baseline γ-glutamyltransferase and its early increase are associated with a poor prognosis in metastatic renal cell carcinoma patients receiving nivolumab. Serum γ-glutamyltransferase levels may help predict treatment outcomes.


Yudai Ishiyama, Tsunenori Kondo, Hidekazu Tachibana, Hiroki Ishihara, Hironori Fukuda, Kazuhiko Yoshida, Toshio Takagi, Junpei Iizuka, Kazunari Tanabe. Predictive role of γ-glutamyltransferase in patients receiving nivolumab therapy for metastatic renal cell carcinoma. International journal of clinical oncology. 2021 Mar;26(3):552-561

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PMID: 33135126

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