Oral Presentation

Immune Checkpoint Inhibitor-Based Downstaging Therapy for HCC Beyond the Milan Criteria: A Multicentre, Retrospective, Matched Cohort Study on Post-Liver Transplant Outcomes

Presenter

Meiching Ong (CN)

The First Affiliated Hospital, Zhejiang University School of Medicine · Hangzhou

Profile

Authors

Meiching Ong^1,2, Feng Wang³, Ziqiang Li⁴, Yipeng Pan⁵, Wenlei Li⁶, Jun Fang^1,2, Aibo Mu^1,2, Zhaoxian Li⁴, Siyi Zhong⁷, Zebin Zhu⁸, Songming Li⁹, Tielong Wang⁹, Xuanyi Zhu⁸, Shugeng Zhang⁸, Zhiyong Guo⁹, Jinzhen Cai³, Jian Xu⁵, Qiang Xia¹⁰, Shusen Zheng^1,2,7,11, Kang He¹⁰, Guangming Li⁶, Qi Ling^1,2,11

Affiliations

¹ First Affiliated Hospital, Zhejiang University School of Medicine

² First Affiliated Hospital, Zhejiang University School of Medicine

³ The Affiliated Hospital of Qingdao University

⁴ Qianfoshan Hospital, Shandong University

⁵ The Second Affiliated Hospital of Hainan Medical University

⁶ YouAn Hospital Affiliated to Capital Medical University

⁷ Shulan (Hangzhou) Hospita

⁸ The First Affiliated Hospital of USTC

⁹ The First Affiliated Hospital, Sun Yat-sen University

¹⁰ Renji Hospital, School of Medicine, Shanghai Jiao Tong University

¹¹ Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, National Medical

Abstract

Introduction: The role of immune checkpoint inhibitor (ICI)-based downstaging before liver transplantation (LT) for hepatocellular carcinoma (HCC) beyond the Milan criteria remains uncertain, particularly regarding post-transplant oncologic benefit versus rejection risk.
Methods: We conducted a multicentre retrospective cohort study across eight high-volume centres in China, including adults with HCC beyond the Milan criteria who received downstaging therapy and ultimately underwent LT between 2019 and 2024. Patients were classified according to pretransplant ICI exposure. Propensity score matching generated 231 patients per group. Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Secondary endpoints included radiologic response by mRECIST, successful downstaging to within the Milan criteria, pathological response, acute rejection, and post-transplant recurrence.
Results: Compared with the non-ICI group, the ICI group achieved higher objective response rate (47.6% vs 20.8%), disease control rate (91.8% vs 80.1%), successful downstaging to within the Milan criteria (14.3% vs 8.2%), pathological complete response (2.6% vs 0%), and major pathological response (28.6% vs 19.0%). Acute rejection was more frequent after ICI exposure (16.0% vs 7.8%, p = 0.006). Despite this, the ICI group had superior post-transplant outcomes, including improved RFS (HR 1.38, 95% CI 1.03-1.84; p=0.033), lower recurrence risk (sHR 1.46, 95% CI 1.09-1.94; p = 0.011), and better OS (HR 1.45, 95% CI 1.03-2.04; p = 0.034). In multivariable analyses, non-ICI treatment remained independently associated with worse RFS, worse OS, and higher recurrence risk. Benefit appeared more pronounced in patients with AFP > 400 ng/mL and tumour number > 3.
Conclusion: In patients with HCC beyond the Milan criteria who ultimately underwent LT, pretransplant ICI-based multimodal downstaging was associated with improved tumour response and more favourable post-transplant oncologic outcomes, despite increased acute rejection. These findings support carefully selected use of ICI-based downstaging, particularly in patients with high-risk tumour biology.

Figure 1. Kaplan-Meier and cumulative incidence curves for post-transplant outcomes after propensity score matching. (A) Recurrence-free survival. (B) Recurrence. (C) Overall survival.

Figure 2. Forest plots for post-transplant outcomes after propensity score matching. (A) Overall survival. (B) Recurrence-free survival. (C) Recurrence.