Immune checkpoint inhibitors after liver transplantation: The role of immunosuppressive management.

The use of immune checkpoint inhibitors (ICIs) after liver transplantation (LT) remains controversial due to rejection risk. This study aims to characterize patients receiving ICIs post-LT and identify the risk factors for rejection. This retrospective, multicenter study included patients who received at least one ICI (anti-programmed cell death 1, anti-programmed cell death ligand 1, or anti-cytotoxic T cell-associated protein 4) post-LT. Fifty-two patients were included (77% male), median age 66 (interquartile range [IQR], 57.5-69.7) years at ICI initiation. The median interval between LT and ICI was 4.5 (IQR, 2.6-9.9) years. ICIs were administered for hepatocellular carcinoma recurrence (62%) or de novo cancer (38%), with similar rejection and survival rates. Rejection occurred in 7 patients (13%) and was moderate/severe, developing at a median of 27 (IQR, 23-57) days post-ICI. The increase of immunosuppression and calcineurin inhibitor use at ICI initiation was associated with reduced rejection risk (P = .04 and P = .013, respectively). Rejection was associated with significantly lower survival (P = .0003). Overall survival following the introduction of ICI at 3, 6, and 12 months was 65%, 46.9%, and 38.9%, respectively. Rejection post-ICI occurs less frequently than previously reported, but early after therapy initiation, it is severe and linked to the absence of calcineurin inhibitors. Optimizing immunosuppression may enhance the safety of ICI use in transplant recipients.