Utilization of immunotherapy as a neoadjuvant treatment in liver transplant recipients with hepatobiliary carcinoma.

Abstract

570 Background: Hepatobiliary Carcinoma (HBC) ranks as the sixth most prevalent cancer worldwide. This study reports our institutional experience in patients with HBC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This retrospective cohort included 25 patients with HBC (17 with HCC, 7 with intrahepatic cholangiocarcinoma (IHCCA), and 1 with perihilar cholangiocarcinoma (PCCA) who received ICPI prior to OLT at a single institution from January 2019 to December 2024. Results: Twenty-five patients with HBC underwent OLT after neoadjuvant ICPI. Nineteen patients were male and 6 were female with a median age of 55 (interquartile range: 36–74) years at OLT. Etiologies included viral hepatitis (N = 8) or non-alcoholic steatohepatitis (NASH) (N = 6), ethanol (ETOH) cirrhosis (N = 1), chronic cholecystitis (N = 2), protein kinase cAMP-activated catalytic subunit alpha (PRKACA) gene rearrangement (N = 1), secondary biliary cirrhosis (N = 1), primary sclerosing cholangitis (N = 1), and unknown (N = 5). Tumor focality was multifocal in seventeen patients and unifocal in eight. Lymphovascular invasion was identified in ten patients while perineural invasion was noted in four patients. All patients received ICPI including combinations of PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors. Liver-directed/ locoregional therapies were utilized in most cases, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 4.5 months. All patients responded to ICPI and achieved a safe and successful OLT. Most patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT with seventeen patients requiring additional IS including prednisone or everolimus. One patient experienced immediate graft failure on the day of transplant, was made anhepatic, and successfully retransplanted the following day. Three patients experienced acute rejection during the first-year post-transplant (2 with liver rejection and 1 with kidney rejection following a deceased donor kidney transplant that was performed in conjunction with OLT). Conclusions: Our study highlights the potential of ICPI to achieve tumor downstaging prior to OLT in patients with HBC when given as a neoadjuvant therapy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, these findings lay the groundwork for prospective trials to further examine the impact of ICPI in the pre-transplant setting.