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

Abstract

Background and aims: Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced HCC patients awaiting liver transplantation (LT). However, concerns about the risk of posttransplant rejection persist.

Approach and results: 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 posttransplant recurrence with a 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 <30 days (OR: 21.3, 95% CI: 5.93-103, p< 0.001) and between 30 and 50 days (OR: 9.48, 95% 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 posttransplantation at 36 months (71% vs. 67%, p =0.71).

Conclusions: Our findings suggest that a washout period longer than 50 days for ICIs before LT 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.

Keywords: HCC; immune checkpoint inhibitor; liver transplantation; recurrence; rejection.