Der Einsatz der immunonkologischen Therapie beim hepatozellulären Karzinom im Kontext der Lebertransplantation Eine interdisziplinäre Risiko-Nutzen-Abwägung

Zusammenfassung

Hintergrund Für das fortgeschrittene hepatozelluläre Karzinom steht uns seit Kurzem ein deutlich erweitertes Spektrum an systemischen Therapieoptionen zur Verfügung. Insbesondere mit den immunonkologischen Kombinationstherapien können mittlerweile beeindruckende Ansprechraten und ein deutlich verlängertes Überleben bei insgesamt guter Verträglichkeit erreicht werden. Dabei werden diese Immun-Onkologie (IO)-basierten Kombinationen nicht nur zur Therapie des fortgeschrittenen HCC geprüft, sondern zunehmend auch in früheren Stadien im Sinne von periinterventionellen Therapiekonzepten und auch zum down-sizing zu lokalen Therapien. Im Kontext der Lebertransplantation (LTx) muss allerdings eine besonders kritische Nutzen-Risiko-Abwägung vor Einsatz von Immuntherapeutika im Rahmen multimodaler Konzepte erfolgen, da durch die Immuntherapie das Risiko einer potenziell letalen Abstoßung signifikant gesteigert werden kann.

Methode Diese Übersichtsarbeit basiert auf einer selektiven Literaturrecherche, die zwischen Dezember 2020 und April 2021 in den Datenbanken PubMed und Cochrane Library durchgeführt wurde. Leitlinien, Expertenmeinungen und Empfehlungen von Fachgesellschaften wurden besonders berücksichtigt.

Ergebnisse Fast jede fünfte LTx in Deutschland erfolgt aufgrund eines HCC (DSO Jahresbericht 2019). Die LTx ist dabei eine kurative Therapieoption nicht nur für die zugrunde liegende Lebererkrankung, sondern auch für den malignen Tumor. Einzelfallbeschreibungen weisen darauf hin, dass auch eine IO-Therapie vor einer LTx das Risiko einer Abstoßung bzw. eines Leberversagens bei einer nachfolgenden LTx erhöhen kann. Seit ca. 2015 werden Immuntherapeutika vielfach auch zur Tumortherapie bei Patienten nach einer LTx eingesetzt. In kleinen Fallserien wurden dabei Abstoßungsraten von 36%, die mit einer abstoßungsbedingten Mortalität von 20% der behandelten Patienten einhergingen, beschrieben. Eine ähnliche Inzidenz von Abstoßungsreaktionen wurde auch nach dem Einsatz von Immuntherapeutika bei Patienten nach anderen Organtransplantationen beschrieben.

Schlussfolgerung Im Zusammenhang mit einer Organtransplantation besteht durch eine IO-Therapie das Risiko einer Transplantatabstoßung, welches zum Verlust des Transplantates und auch zum Tod des Patienten führen kann. Unter Abwägung der oben dargelegten Überlegungen kann aber nach unserer sorgfältigen Nutzen-Risiko-Abwägung aus heutiger Sicht ein Einsatz einer IO-basierten Therapie im Kontext der Organtransplantation erfolgen.

Abstract

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, IO therapy carries the risk of graft rejection, which can lead to graft loss and also patient death. However, from today’s point of view, IO-based therapy can be considered in the context of organ transplantation with a careful benefit/risk assessment.

Schlüsselwörter

Nivolumab - Pembrolizumab - Ipilimumab - Rejektion - Transplantatversagen

Keywords

Nivolumab - Pembrolizumab - Ipilimumab - rejection - transplant failure

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