Prognostic Significance of Tumor-Cell VISTA Expression on Survival Outcomes in Nivolumab-Treated Pleural Mesothelioma: The HOT1901 Retrospective Multi-Institutional Study

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Background: Nivolumab is used as a second-line treatment for pleural mesothelioma (PM); however, predictive or prognostic biomarkers remain unclear. We aimed to identify factors associated with survival in nivolumab-treated PM patients. Methods: This retrospective, multi-institutional cohort study included patients with PM who received nivolumab monotherapy as a second-line or later treatment at 18 hospitals in Japan. We evaluated associations of progression-free survival (PFS) and overall survival (OS) with baseline clinical variables, protein expression in tumor tissue specimens obtained before first-line therapy by immunohistochemical (IHC), and tumor mutational and copy-number profiles detected by next-generation sequencing (NGS). Results: Fifty-five patients were enrolled, with evaluable IHC in 42 and NGS in 33. V-domain immunoglobulin suppressor of T-cell activation (VISTA) expression was classified as high or low using a cutoff of 10% VISTA-positive tumor cells. High VISTA expression (n=35) was significantly associated with improved PFS and OS compared with low expression (n=7) (PFS: median, 5.1 vs 2.4 months, p = 0.001; OS: median, 12.8 vs 4.3 months, p = 0.007). Multivariate analysis confirmed high VISTA expression as an independent predictor of prolonged PFS and OS (PFS: hazard ratio [HR] 0.14, p < 0.001; OS: HR 0.38, p = 0.044). Conclusion: Low tumor-cell VISTA expression was associated with poorer outcomes following nivolumab treatment; however, independent validation in prospective studies with a comparator arm is required before VISTA expression can be used to guide treatment selection. These findings support further investigation of biomarkers for combination strategies such as nivolumab-ipilimumab or chemoimmunotherapy in PM.

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