Scientific publications
Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis
Mohammad Saeid Rezaee-Zavareh 1 , Yee Hui Yeo 2 , Tielong Wang 3 , Zhiyong Guo 3 , Parissa Tabrizian 4 , Stephen C Ward 5 , Fatma Barakat 6 , Tarek I Hassanein 6 , Dave Shravan 7 , Ajmera Veeral 7 , Sherrie Bhoori 8 , Vincenzo Mazzaferro 9 , David M H Chascsa 10 , Margaret C Liu 11 , Elizabeth S Aby 12 , John R Lake 12 , Miguel Sogbe 13 , Bruno Sangro 13 , Maen Abdelrahim 14 , Abdullah Esmail 15 , Andreas Schmiderer 16 , Yasmina Chouik 17 , Mark Rudolph 18 , Davendra Sohal 18 , Heloise Giudicelli 19 , Manon Allaire 20 , Mehmet Akce 21 , Jessica Guadagno 22 , Clara Y Tow 23 , Hatef Massoumi 24 , Paolo De Simone 25 , Elise Kang 26 , Robyn D Gartrell 27 , Mercedes Martinez 28 , Ricardo Paz-Fumagalli 29 , Beau B Toskich 30 , Nguyen H Tran 31 , Gabriela Azevedo Solino 32 , Dra Mariana Poltronieri Pacheco 33 , Richard S Kalman 34 , Vatche G Agopian 35 , Neil Mehta 36 , Neehar D Parikh 37 , Amit G Singal 38 , Ju Dong Yang 39
Background and aim: 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.
Materials and methods: 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.
Results: Among 91 eligible patients, with a median (interquartile range [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% confidence interval [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) CONCLUSION: 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.
Impact and implications: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests 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 ICI 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. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.
CITATION J Hepatol. 2024 Jul 10:S0168-8278(24)02354-7. doi: 10.1016/j.jhep.2024.06.042
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