Graft PD-L1 expression as a marker for transplant rejection following anti-PD1 immunotherapy for recurrent liver tumors.

Emerging evidence supports a role for immune checkpoint inhibitor therapy in addition to standard chemotherapy and/or targeted therapy for advanced malignancy. However, transplant patients usually are excluded from immune checkpoint inhibitor therapy due to the fear of possible graft rejection. We aimed to confirm that the lack of graft PD-L1 expression is a biomarker for the safety of using anti-PD1 therapy for liver transplant patients who suffered disease recurrence. We conducted a prospective, single-arm study of patients with recurrent hepatic tumors following liver transplantation whose allograft demonstrated absence of PD-L1 expression by immunohistochemistry (IHC) at Zhongshan Hospital. Participants who received a liver transplantation for hepatocellular carcinoma (HCC) or biliary tract cancers and experienced tumor recurrence or secondary primary hepatic malignancy were screened for PD-L1 expression in graft. Eligible patients (negative PD-L1 expression in graft) received toripalimab, 240mg every 3 weeks until graft rejection, grade 4 or unacceptable toxicity, or voluntary withdrawal. The primary study objective was to compare the graft rejection rate for liver (PD-L1 negative graft) transplant recipients receiving PD1 inhibitor to historical controls (liver transplant recipients with unknown PD-L1 status). The study was registered with ClinicalTrials.gov (NCT03966209). All the 5 patients without PD-L1 expression in their grafts received anti-PD1 therapy without developing graft-related immune-related adverse events (irAEs). One off study patient with positive graft PD-L1 expression suffered graft rejection. CONCLUSIONS: Graft PD-L1 expression may be a promising marker for transplant recipients' organ rejection following anti-PD1 immunotherapy. These findings need to be further investigated in patients with solid organ transplantation.