Immune checkpoint inhibitors as a neoadjuvant therapy pre-liver transplantation for hepatobiliary carcinoma.

e14624Background: Hepatobiliary carcinoma (HBC) is the sixth most prevalent cancer worldwide, with hepatocellular carcinoma (HCC) being the most common primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment for early-stage HBC. In the evolving era of transplant oncology, immunotherapies are actively being investigated as neoadjuvant strategies to improve patient outcomes. This study reports our institutional experience with patients who received immune checkpoint inhibitors (ICPI) prior to curative OLT. Methods: This retrospective cohort study included 25 patients with HBC who received ICPI before undergoing OLT at a single institution between January 2019 and December 2024. The cohort comprised 17 patients with HCC, 7 with intrahepatic cholangiocarcinoma (IHCCA), and 1 with perihilar cholangiocarcinoma (PCCA). Graft rejection, tumor characteristics, locoregional therapies (LRTs), ICPI regimens, and timing of ICPI administration relative to OLT were evaluated. Results: Among the 25 patients who underwent OLT following neoadjuvant ICPI, 19 were male and 6 were female, with a median age of 55 years (interquartile range: 36–74). Underlying liver disease etiologies included viral hepatitis (n = 8), non-alcoholic steatohepatitis (NASH) (n = 6), ethanol-induced cirrhosis (n = 1), chronic cholecystitis (n = 2), PRKACA (protein kinase cAMP-activated catalytic subunit alpha) gene rearrangement (n = 1), secondary biliary cirrhosis (n = 1), primary sclerosing cholangitis (n = 1), and unknown causes (n = 5). Tumor focality was multifocal in 17 patients and unifocal in 8. Lymphovascular invasion was present in 10 cases, and perineural invasion was noted in 4. All patients received ICPI, including combinations of PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors. Most patients also underwent liver-directed LRTs, including transarterial chemoembolization (TACE), Yttrium-90 (Y90) radioembolization, stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period before OLT was 4 months. All patients demonstrated tumor response to ICPI and successfully proceeded to OLT. Post-transplant immunosuppression primarily consisted of tacrolimus plus mycophenolate, with 17 patients requiring additional immunosuppression, including prednisone or everolimus. Notably, no cases of graft rejection were observed in the study cohort. Conclusions: Our findings highlight the potential of ICPI as an effective neoadjuvant therapy for tumor downstaging prior to OLT in patients with HBC. Additionally, this study underscores the importance of optimizing the timing of ICPI administration before transplantation. Given the limited conclusive evidence in this therapeutic area, our results provide a foundation for prospective trials to further evaluate the role of ICPI in the pre-transplant setting.