An immune checkpoint inhibitor–based multimodal downstaging strategy before liver transplantation was associated with improved posttransplant survival and a lower risk of recurrence among patients with hepatocellular carcinoma initially beyond the Milan criteria (single lesion not larger than 5 cm or two or three lesions not larger than 3 cm each), based on findings from a Chinese study published in JAMA Oncology. However, according to Ong et al, the strategy was also associated with a higher rate of acute rejection within 90 days posttransplantation.
“By characterizing this post–liver transplantation benefit-risk profile, this multicenter matched cohort study may inform future prospective studies of immune checkpoint inhibitor–based pretransplant strategies in liver transplantation candidates and help clinical decision-making,” the investigators wrote.
Study Details
The investigators retrospectively evaluated patients with hepatocellular carcinoma initially beyond the Milan criteria who underwent liver transplantation at eight high-volume centers (> 55 liver transplantations annually) in China between January 2019 and December 2024. Propensity score matching was used to balance measured covariates between patients who received an immune checkpoint inhibitor–based multimodal strategy before transplantation (typically combined with locoregional and/or targeted therapies) and those who received treatment without immune checkpoint inhibitors.
The matched cohort included 416 transplant recipients, with 208 each in the investigational and comparator groups.
The primary outcomes were overall survival and recurrence-free survival following transplantation. Secondary outcomes included posttransplant recurrence and acute rejection within 90 days.
Key Findings
Median overall survival was longer with the immune checkpoint inhibitor–based multimodal pretransplant strategy vs therapy without immune checkpoint inhibitors (4.6 vs 2.5 years; P < .001). Median recurrence-free survival was 1.5 and 0.9 years, respectively (P = .02).
Multivariable Cox analyses showed that the immune checkpoint inhibitor–based multimodal pretransplant strategy was associated with improved overall survival (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43–0.92) and recurrence-free survival (HR = 0.59, 95% CI = 0.44–0.80). Based on a Fine-Gray model, the strategy was associated with a lower risk of posttransplant recurrence (subdistribution HR = 0.54, 95% CI = 0.40–0.72).
Patients treated with the immune checkpoint inhibitor–based multimodal pretransplant strategy had a higher rate of acute rejection within 90 days of liver transplantation compared with those who received therapy without immune checkpoint inhibitors (16.3% vs 8.2%; P = .01).
“The results of this cohort study suggest that an immune checkpoint inhibitor–based multimodal pretransplant strategy was associated with better posttransplant oncologic outcomes and survival in selected patients with hepatocellular carcinoma that was initially beyond the Milan criteria, despite more frequent acute rejection,” the investigators concluded.
Looking ahead, they wrote, “Prospective multicenter studies and randomized clinical trials are needed to validate these findings and determine how this strategy should be integrated into transplant candidate selection and peritransplant rejection risk management.”
Qi Ling, MD, PhD, of The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, and Guangming Li, MD, of YouAn Hospital, Capital Medical University, Beijing, are the corresponding authors of the article in JAMA Oncology.
Disclosure: The study was supported by grants from the National Science and Technology Major Projects and the Leading Goose Research and Development Program of Zhejiang Province. The study authors reported no conflicts of interest.
