Determining safe washout period for immune checkpoint inhibitors prior to liver transplantation: An international retrospective cohort study

Immune checkpoint inhibitors (ICI) are increasingly used in patients with advanced hepatocellular carcinoma (HCC) patients awaiting liver transplantation (LT). However, concerns about the risk of post-transplant rejection persist. We conducted an international retrospective cohort study including 119 HCC patients who received ICIs prior to LT. We analyzed the incidence of allograft rejection, graft loss, and post-transplant recurrence with particular focus on the washout period between the last ICI dose and LT. In this study, 24 of the 119 (20.2%) patients experienced allograft rejection with a median time to rejection of 9 days (IQR 6-10) post-LT. A linear relationship was observed between shorter washout periods and higher rejection risk. Washout periods less than 30 days (OR 21.3, 95% CI: 5.93-103, p<0.001) and between 30 and 50 days (OR 9.48, CI 2.47-46.8, p=0.002) were significantly associated with higher rejection rates in the univariate analysis compared to the washout period above 50 days. Graft loss as a result of rejection occurred in 6 patients (25%) with rejection. No factors related to grafts were associated with rejection. A longer washout period was not associated with a lower recurrence-free survival post-transplantation at 36 months (71 vs. 67%, p=0.71). Our findings suggest that a washout period longer than 50 days for ICIs before liver transplantation appears to be safe with respect to rejection risk. While these results may help guide clinical decision-making, future prospective studies are essential to establish definitive guidelines.