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