The use of immuno-oncologic therapy in hepatocellular carcinoma in the context of liver transplantation. An interdisciplinary benefit/risk assessment

Background Multiple systemic therapy options have been recently approved for the treatment of hepatocellular carcinoma (HCC). In particular, immuno-oncology combination therapies can now achieve impressive response rates and significantly prolonged survival with good tolerability. These immuno-oncology (IO)-based combinations are currently not only evaluated for the therapy of advanced HCC, but increasingly also in earlier stages in terms of peri-interventional therapy concepts and also for down-sizing to local therapies. In the context of liver transplantation (LTx), a particularly critical benefit/risk assessment must be made before the use of immunotherapeutics in the context of multimodal concepts, since the risk of a potentially lethal rejection can be significantly increased by immunotherapy. Methods This review is based on a selective literature search performed between December 2020 and April 2021 in the PubMed and Cochrane Library databases. Guidelines, expert opinions, and recommendations from professional societies were given special consideration. Results Nearly one in five LTx in Germany are performed due to HCCs. In this context, LTx is a curative therapy option not only for the underlying liver disease but also for the malignant tumor. Individual case reports indicate that IO therapy prior to LTx may increase the risk of rejection or liver failure after subsequent liver transplantation. Since 2015, immunotherapeutics have also been widely used for tumor therapy in patients after LTx. In small case series, rejection rates of 36%, associated with rejection-related mortality of 20 % of treated patients, have been described. A similar incidence of rejection has also been described following the use of immunotherapeutics in patients after other organ transplantations. Conclusion In the context of organ transplantation, 10 therapy carries the risk of graft rejection, which can lead to graft loss and also patient death. However, from today's point of view,10-based therapy can be considered in the context of organ transplantation with a careful benefit/risk assessment.