Efficacy of immune checkpoint inhibitors in patients with HIV-associated unresectable HCC (uHCC): Propensity-score matched analyses from two international consortia.
Authors: Fulgenzi Claudia A.M. , El Zarif Talal , Nassar Amin , Adib Elio , Bellmunt Joaquim , Marron Thomas Urban , Lorentsen Michael , McKay Rana R. , Baena Javier , Ang Celina , Rimassa Lorenza , Kudo Masatoshi , Parisi Alessandro , Saeed Anwaar , Lee Pei-Chang , Parikh Neehar , Pinter Matthias , Cortellini Alessio , Naqash Abdul Rafeh , Pinato David James 
Published: January 2024

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Background: HIV-associated HCC is an incompletely characterized disease with poor prognosis. People living with HIV (PWH) are commonly excluded from clinical trials, leading to a paucity of high-level evidence for optimal management. Whether ICIs are tolerated and effective in HIV-associated uHCC remains unclear. Methods: Using data from the CATCH-IT consortium and from a global dataset recruiting patients with HCC from 14 centers in 3 continents, we selected patients with HIV-associated uHCC treated with ICIs and compared their outcomes with a matched cohort of HIV negative (HIV-) patients. Primary endpoints were overall (OS) and progression-free survival (PFS). Propensity score matching (PSM) between the two groups was performed for the following variables: age, sex, HCC aetiology, Child-Pugh class (CP-C), ECOG-PS, BCLC stage, alpha-fetoprotein (AFP) levels, treatment line, portal vein tumor thrombosis (PVTT), and extrahepatic spread (EHS). Restricted mean survival time (RMST) difference analyses stratified by HIV status were performed for OS and PFS at 3, 6 and 9 months. Results: We accrued 46 PWH and 400 HIV-, treated mostly in the first-line setting (58.7% vs. 43.7%) with either atezolizumab plus bevacizumab (28.3% vs 17.5%) or anti-PD-1 monotherapy. Median age at ICI start was 62 (38-76) and 64 (18-87); viral hepatitis (HCV: 58.7%; HBV: 34.8%) were the prevalent aetiologies in PWH, non-viral (46%) was the most common in HIV-; most patients had BCLC-C HCC (84.8% and 82.3%). In PWH, median CD4 count was 345 cells/mm3 (IQR: 200-465); viral load was undetectable in 45 patients, all were established on combined anti-retroviral therapy. Following PSM, 44 PWH and 117 HIV- were included. Median OS was 7.5 months (95%CI: 5.2-NR) in PWH and 10.8 months (95%CI: 7.3-19.5) in HIV- (HR: 0.89; 95%CI: 0.56-1.42; p=0.58). Presence of PVTT, AFP>400 ng/mL, and ECOG-PS=1 but not HIV status were associated with worse OS in uni- and multivariable models. Median PFS was 2.8 months (95%CI: 2.6-4.8) for PWH vs 3.0 months (95%CI: 2.4-5.3) for HIV- (HR: 0.83-95%CI:0.56-1.24 ;p=0.38); HIV status was not associated with worse PFS. RMST confirmed no OS or PFS differences based on HIV status. In matched cohorts, neither ORR (21% vs. 19.1%, p=0.97) nor DCR (44.7% vs. 55.4%, p=0.19) were associated with HIV status. All grade immune-related adverse events (irAEs) were more frequent in HIV (44.0% vs 21.7%, p=0.003), with similar incidence of grade ≥3 irAEs (22.2% vs 13.0%). PWH had lower incidence of dermatological toxicities (4.3% vs 22%, p=0.003) and a trend towards lower incidence of hepatotoxicity (6.5% vs 18%, p=0.059). Conclusions: This study provides practice-informing evidence to support the use of ICIs in PWH and uHCC. Our findings encourage the inclusion of patients with well-controlled HIV in prospective clinical trials.