Safety of immunotherapy after liver transplantation-A multicenter study of a prospective standardized clinical practice protocol.

Immune checkpoint inhibitors (ICIs) have improved cancer prognosis significantly, but their use has been avoided in liver transplant recipients (LTr) due to poorly characterized rejection risk. Data surrounding rejection risk are extremely suboptimal, with highly variable immunosuppression approaches and follow-up, and do not account for the learning curve in managing immunosuppression in the setting of ICI. A standardized institutional clinical practice protocol was developed in 2021 for immunosuppression management to facilitate ICI therapy with prospective close follow-up for immunosuppression levels and allograft function. Of 20 LTr, 12 (60%) were male, 18 (90%) were Caucasian, with a mean age of 54.0 (SD 11.2) years. However, 13/20 had 2 or more failed cancer therapies before ICI. Hepatocellular carcinoma ​(HCC) (N=7), lung (N=3), and melanoma (N=3) were the most frequent. Time from first ICI treatment to death was <30 days (N=5), 30-59 days (N=4), 60-89 days (N=1), and >90 days (N=6). Most deaths were cancer-related, reflecting the late stage of disease. ICI toxicity occurred in 3 LTr; pneumonitis (N=1, 5%), myocarditis (N=1, 5%), and acute cellular rejection (N=1, 5%). Four patients remain alive 178-341 days with stable allograft function and slow reduction in immunosuppression. Three out of 4 patients have a partial cancer response, and 1 with slowed progression of disease. ICI treatment in the immunosuppressed LTr is feasible with careful immunosuppression management and follow-up. Demonstrating a low rejection risk should allow for earlier utilization of these agents to improve cancer prognosis. Optimizing rejection risk with cancer response requires ongoing study.