Long Teng, Yang Zhenyun, Wu Weijie, Chen Minshan, Hu Dandan
Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510000, Guangdong, China.
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou 510000, Guangdong, China.
ILIVER. 2025 May 16;4(2):100169. doi: 10.1016/j.iliver.2025.100169. eCollection 2025 Jun.
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.
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).
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.
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.
本研究旨在评估程序性细胞死亡蛋白1（PD-1）抑制剂免疫疗法在代谢功能障碍相关脂肪性肝病（MAFLD）相关肝内胆管癌（ICC）患者中的疗效和安全性，并与无MAFLD的患者进行比较。
我们回顾性纳入了161例接受PD-1抑制剂治疗的ICC患者，其中包括有和没有MAFLD的患者，治疗时间为2019年3月至2024年8月。允许进行后续的局部区域干预（如肝动脉灌注化疗）和二线全身治疗药物（如乐伐替尼）。主要终点包括总生存期（OS）和无进展生存期（PFS），次要终点包括客观缓解率（ORR）、疾病控制率（DCR）和不良事件（AE）。
MAFLD组包括20例患者，非MAFLD组包括141例患者。MAFLD组的OS为18.0个月，非MAFLD组为20.1个月，中位PFS分别为8.0个月和11.5个月。根据改良RECIST（mRECIST）标准，非MAFLD组显示出更大的临床获益，表现为更高的ORR和DCR（45.4%对20.0%，P = 0.031；92.9%对75.0%，P = 0.024）。多因素Cox比例风险分析确定癌胚抗原（CEA）、肿瘤数量和C反应蛋白（CRP）为OS的独立预后因素，而CEA和肿瘤数量是PFS的显著预测因素。此外，非MAFLD组AE的总体发生率明显低于MAFLD组。
本研究表明，PD-1抑制剂在有和没有MAFLD的ICC患者中导致相似的OS和PFS延长，但在没有MAFLD的患者中观察到更好的肿瘤反应。此外，非MAFLD组接受PD-1抑制剂治疗时AE的发生率明显低于MAFLD组。
