Graft PD-L1 as a predictive marker for rejection in PD-1 inhibitor therapy for recurrent liver tumors post-transplant: A prospective pilot trial

The safety of immunotherapy in transplant patients remains unclear due to rejection risks. This study assessed the safety and efficacy of programmed death-1 (PD-1) inhibitors in post liver-transplantation patients with recurrent tumors, emphasizing the value of using graft programmed death-ligand 1 (PD-L1) expression as a predictor of rejection to guide patient selection. This single-center, open-label, prospective, single-arm study was conducted from July 2019 to May 2024 at Zhongshan Hospital, Fudan University (Shanghai, China). Eligible participants included post liver-transplantation patients with recurrent or metastatic liver cancer who were unresponsive to locoregional or systemic therapies. The primary endpoints were the incidence and clinical outcomes of acute rejection. Secondary endpoints were overall survival and objective response rate. Twenty consecutive patients received PD-1 inhibitor therapy. Of these, 18 had hepatocellular carcinoma, and two had intrahepatic cholangiocarcinoma. Liver graft biopsies confirmed negative PD-L1 expression in all participants before PD-1 inhibitor therapy. Three patients (15%) experienced acute rejection, with a 95% CI of 3.2–37.9%. The 1-year and 2-year survival probabilities after PD-1 inhibitor treatment were 0.55 (95% CI 0.33–0.77) and 0.24 (95% CI 0.05–0.43), respectively. The median survival time after tumor recurrence was 24.6 months, exceeding the historically reported median survival time of 16.3 months. These exploratory findings suggest that, in selected liver transplant recipients, PD-1 inhibitors may be associated with reduced rejection risk and potential survival benefit, although further validation is needed.