Efficacy and safety of PD-1 inhibitors for advanced intrahepatic cholangiocarcinoma with or without MAFLD.

Background: This study sought to evaluate the efficacy and safety of programmed cell death protein-1 (PD-1) inhibitor immunotherapy specifically in metabolic dysfunction-associated fatty liver disease (MAFLD)-associated intrahepatic cholangiocarcinoma (ICC) patients, in comparison to those without MAFLD. Methods: We retrospectively included 161 ICC patients, both with and without MAFLD, who underwent PD-1 inhibitors between March 2019 and August 2024. Subsequent locoregional interventions (e.g., hepatic arterial infusion chemotherapy) and second-line systemic agents (e.g., lenvatinib) were allowed. The primary endpoints included overall survival (OS) and progression-free survival (PFS), while the secondary endpoints comprised objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results: The MAFLD group included 20 patients, while the Non-MAFLD group comprised 141 patients. The OS was 18.0 months for the MAFLD group and 20.1 months for the Non-MAFLD group, while the median PFS was 8.0 and 11.5 months, respectively. According to the modified RECIST (mRECIST) criteria, the Non-MAFLD group exhibited a greater clinical benefit, reflected in higher ORR and DCR (45.4% vs. 20.0%, Conclusion: This study demonstrated that PD-1 inhibitors resulted in similarly prolonged OS and PFS between ICC patients with and without MAFLD, but a superior tumor response was observed in patients without MAFLD. Additionally, the Non-MAFLD group experienced a significantly lower incidence of AEs than the MAFLD group undergoing PD-1 inhibitors.