Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis

• Published in: Journal of hepatology
• Main Authors: Rezaee-Zavareh, Mohammad Saeid, Yeo, Yee Hui, Wang, Tielong, Guo, Zhiyong, Tabrizian, Parissa, Ward, Stephen C., Barakat, Fatma, Hassanein, Tarek I., Dave, Shravan, Ajmera, Veeral, Bhoori, Sherrie, Mazzaferro, Vincenzo, Chascsa, David M.H., Liu, Margaret C., Aby, Elizabeth S., Lake, John R., Sogbe, Miguel, Sangro, Bruno, Abdelrahim, Maen, Esmail, Abdullah, Schmiderer, Andreas, Chouik, Yasmina, Rudolph, Mark, Sohal, Davendra, Giudicelli, Heloise, Allaire, Manon, Akce, Mehmet, Guadagno, Jessica, Tow, Clara Y., Massoumi, Hatef, De Simone, Paolo, Kang, Elise, Gartrell, Robyn D., Martinez, Mercedes, Paz-Fumagalli, Ricardo, Toskich, Beau B., Tran, Nguyen H., Solino, Gabriela Azevedo, Poltronieri Pacheco, Dra Mariana, Kalman, Richard S., Agopian, Vatche G., Mehta, Neil, Parikh, Neehar D., Singal, Amit G., Yang, Ju Dong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.07.2024
• Subjects: Graft Rejection; Hepatocellular Carcinoma; Immune Checkpoint Inhibitors; Liver Neoplasms; Liver Transplantation; Recurrence; Recurrence; Graft Rejection; Liver Transplantation; Liver Neoplasms; Immune Checkpoint Inhibitors; Hepatocellular Carcinoma
• ISSN: 0168-8278; 1600-0641; 1600-0641
• DOI: 10.1016/j.jhep.2024.06.042

Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. Among 91 eligible patients, with a median (IQR) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years 0.72, 95% CI 0.53–0.99, p = 0.044) and ICI washout time (aHR per 1 week 0.92, 95% CI 0.86–0.99, p = 0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p = 0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8] vs. 8.0 [9.0]; p = 0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p = 0.032). Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitor use prior to liver transplantation suggest acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without immune checkpoint inhibitor exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. [Display omitted] •Acceptable risk of allograft rejection, cancer recurrence, and mortality among patients with HCC who receive ICIs prior to LT.•Increased age and ICI washout period were associated with reduced chance of allograft rejection.•A median ICI washout period of 94 days or more was associated with a risk of allograft rejection ≤20%.•Over 80% of allograft rejection was resolved with medical management and overall survival was unaffected.•An increased number of ICI cycles and within Milan criteria post-ICI completion were associated with a lower risk of HCC recurrence.