Yudai Ishiyama1,2, Tsunenori Kondo3, Hidekazu Tachibana1, Hiroki Ishihara2, Hironori Fukuda2, Kazuhiko Yoshida2, Toshio Takagi2, Junpei Iizuka2, Kazunari Tanabe2. 1. Department of Urology, Tokyo Women's Medical University Medical Center East, 2-1-10 Nishiogu, Arakawa-ku, Tokyo, 116-8567, Japan. 2. Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan. 3. Department of Urology, Tokyo Women's Medical University Medical Center East, 2-1-10 Nishiogu, Arakawa-ku, Tokyo, 116-8567, Japan. tsunenori.kondo@twmu.ac.jp.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
INTRODUCTION: γ-Glutamyltransferase is reportedly associated with survival in local and metastatic renal cell carcinomapatients; 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 carcinomapatients undergoing nivolumab therapy. METHODS: We retrospectively evaluated 69 nivolumab-treated metastatic renal cell carcinomapatients 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. RESULTS: 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). CONCLUSIONS: High baseline γ-glutamyltransferase and its early increase are associated with a poor prognosis in metastatic renal cell carcinomapatients receiving nivolumab. Serum γ-glutamyltransferase levels may help predict treatment outcomes.