Background: The vast majority of HCC cases occur in the setting of liver cirrhosis. Patients with decompensated cirrhosis CHILD-Pugh Class B and C (CPB and CPC) are usually excluded from clinical trials. Here we report the safety and tolerability of CPI in patients with CPB/CPC. Methods: A retrospective chart review was performed of all patients with aHCC who received therapy with CPI from 1/2019 to 12/2022 at our institution. Patients with CP class B and C were included in this study. Safety endpoints included rates of immune-related adverse events (irAEs), grade ≥3 adverse events (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 5.0]), duration of treatment with CPI and overall survival (OS) were reported. Results: We performed this retrospective chart review of 60 patients with aHCC who were treated with CPI at our institution. A total of 22 patients with CPB and CPC at the time of CPI initiation were included, 86.4% with CPB (n=19) and 13.6% with CPC (n=3). Median age was 68 (range 40-82). Amongst patients with CPB, 10 patients (45.4%) had CP score 7 (CP7) and 9 patients (40.9%) had CP score 8 or 9. Single agent nivolumab was the most common CPI used, followed by pembrolizumab and combination of ipilimumab and nivolumab, 38.4%, 27.3% and 13.6% respectively. Any grade irAEs were reported in 54.5% of patients (n=12).9% of patients (n=2) had grade ≥3 irAEs. In the CP7 subgroup, the rate of irAEs reported was 40% and no grade ≥3 irAEs were observed. In contrast, 55.5% of patients with CP 8 and 9 experienced irAEs and of those, 11.1% had grade ≥3 irAEs (n=1). In the CPC subgroup, 2 out of 3 patients reported irAEs (75%), one with a grade 4 irAE. GI complications(n=5) were the most common irAEs reported, followed by endocrine (n=4) and dermatologic complications (n=3). The median time on treatment was 1.63 months (95% CI,1.08-2.99). The median overall survival from the time of CPI initiation was 3.7 months (95% CI, 1.97-9.79). Conclusions: Immunotherapy has an acceptable safety and toxicity profile in aHCC patients with CP7. Higher rate of irAEs were observed in patients with CP ≥8. Further studies are warranted to evaluate the safety of CPI in patients with CP ≥8. We reported shorter duration of treatment with CPI and shorter OS in real world practice compared with those reported in the CheckMate 040 trial.

*Steroid avoided due to high HCV viral load.