Multicenter retrospective matched cohort study of immune checkpoint inhibitor-based downstaging therapy for hepatocellular carcinoma

In patients with hepatocellular carcinoma (HCC) that is initially beyond the Milan criteria, immune checkpoint inhibitor (ICI)-based regimens have been explored before liver transplant (LT) to improve tumor control as part of downstaging strategies that most often involve locoregional therapy but associations with posttransplant oncologic and survival benefit are not clear. A retrospective matched cohort study at 8 high-volume LT centers (> 55 LTs annually) investigated the associations of an ICI-based multimodal pretransplant strategy with posttransplant oncologic outcomes and acute rejection among patient with HCC that was initially beyond the Milan criteria. Propensity score matching balanced covariates between ICI and non-ICI groups. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS) from LT. Secondary outcomes were posttransplant recurrence and acute rejection within 90 days. Among 416 matched recipients, 208 received ICI-based multimodal therapy and 208 did not. Median OS was 4.57 years (95% CI 4.34-NE) in the ICI group and 2.53 years (2.17-3.10; p<0.001) in the non-IC group; median RFS was 1.47 years (1.18-4.34) versus 0.89 years (0.75-1.39; p=0.02). In multivariable Cox models, the ICI-based multimodal strategy was associated with better OS (HR 0.63; 95% CI 0.43-0.92) and RFS (0.59; 0.44-0.80). Acute rejection within 90 days was more frequent in the ICI group (16.3% versus 8.2%; p=0.01). The authors conclude that these results suggest that an ICI-based multimodal pretransplant strategy was associated with better posttransplant oncologic outcomes and survival in selected patients with HCC that was initially beyond the Milan criteria, despite more frequent acute rejection.