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%, = 0.031; 92.9% vs. 75.0%, = 0.024). Multivariate Cox proportional hazard analysis identified carcinoembryonic antigen (CEA), tumor number, and C-reactive protein (CRP) as independent prognostic factors for OS, whereas CEA and tumor number were significant predictors of PFS. Additionally, the overall incidence of AEs was notably lower in the Non-MAFLD group compared to the MAFLD group.

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.