Abstract PO003: Combination therapy with Nivolumab/Bevacizumab is safe and effective in patients with recurrent hepatocellular carcinoma after liver transplant

Recurrent hepatocellular carcinoma (HCC-R) after Liver Transplant (LT) is difficult to manage and often characterized by relevant aggressiveness and extrahepatic localizations. Currently TKIs are the only therapeutic option, but results in term of overall survival (OS) and progression-free survival are disappointing. Immune checkpoint inhibitors in association with recombinant humanized monoclonal antibody to VEGF were to be proved effective in non-LT patients with metastatic hepatocellular carcinoma in determining tumor stabilization and improved survival. However, as in LT patients immunotherapy may increase the risk of acute liver rejection, such combination therapy has not been used so far. We designed a proof-of-concept study to analyze safety and efficacy of Nivolumab and Bevacizumab in LT patients as treatment for HCC-R after LT. Combination therapy received nominal authorization from the Provincial Medicines Commission. Candidate patients underwent routine blood test (hepatic, renal, and cardiac function), echocardiogram and a total body CT as baseline assessment. Patients with creatinine higher than 1.5 ULN or with ejection fraction lower than 45% were excluded. Five patients who experienced HCC-R 2 to 8 years after LT with pulmonary, lymph node, adrenal, bones, and hepatic localization and were either intolerant to TKIs or had had progression on TKIs, were included. All recurrent tumors and extra-hepatic localizations were characterized by high biologic aggressiveness. Patients received Nivolumab infusion every 14 days at a dose of 240 mg. Total body CT scan was performed every 8 weeks. When progression disease (PD) was detected at CT scan, Bevacizumab was added at a dose of 5 mg/kg every 14 days. One patient received a single Nivolumab infusion but was withdrawn because of rapid tumor progression, eventually followed by death. Another patient experienced moderate/severe rejection, which resolved with 1g/day Methylprednisolone e.v. for 3[EV1] days followed by Prednisone 50mg/day for 1 week then tapered and stopped. This patient was maintained on double therapy without residual problems. The 4 alive patients are still on double therapy after a mean period of treatment of 36±21 weeks. Disease stability with the combination of Nivolumab/Bevacizumab has been achieved in all patients at hepatic and all extra-hepatic HCC localization but bone, where 2/2 patients experienced progression. It should be underlined, however, that progression was very slow a