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

Background: Hepatobiliary carcinoma (HBC) ranks as the sixth most prevalent cancer worldwide. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for early-stage HBC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era. 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 and eight with cholangiocarcinoma (CCA)], who received ICPI prior to OLT at a single institution from January 2019 to December 2025. Graft rejection was assessed and reported along with the type of ICPI, tumor features, locoregional therapies (LRTs), and the timing of ICPI in association with OLT. Results: All 25 patients with HBC underwent OLT after neoadjuvant ICPI. A total of 19 patients were men, and six were women with a median age of 55 (interquartile range: 36-74) years at OLT. 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 17 patients requiring additional IS, including prednisone or everolimus. One patient experienced immediate graft failure on the day of transplant, was made anhepatic, and was successfully retransplanted on the following day. Three patients experienced acute rejection during the first year post-transplant (two with liver rejection and one 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.