A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C
Sangro B, Gomez-Martin C, de la Mata M, Iñarrairaegui M, Garralda E, Barrera P, Riezu-Boj JI, Larrea E, Alfaro C, Sarobe P, Lasarte JJ, Pérez-Gracia JL, Melero I, Prieto J.
Liver Unit and HPB Oncology, Clinica Universidad de Navarra, Pamplona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd).
Magazine: Journal of Hepatology
Date: Mar 2, 2013Medical Oncology Immunology [SP] Hepatology
BACKGROUND AND AIMS:
Tremelimumab is a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), an inhibitory co-receptor that interferes with T cell activation and proliferation.
The purpose of this pilot clinical trial was to test the antitumor and antiviral effect of Tremelimumab in patients with hepatocellular carcinoma (HCC) and chronic hepatitis C virus (HCV) infection; and to study the safety of its administration to cirrhotic patients.
Tremelimumab at a dose of 15 mg/kg IV every 90 days was administered until tumor progression or severe toxicity. Twenty patients were evaluable for toxicity and viral response and 17 were evaluable for tumor response. Most patients were in the advanced stage and 43% had an altered liver function (Child-Pugh class B).
A good safety profile was recorded and no patient needed steroids because of severe immune-mediated adverse events. Some patients had a transient albeit intense elevation of transaminases after the first dose but not following subsequent cycles. Partial response rate was 17.6% and disease control rate was 76.4%. Time to progression was 6.48 months (95%CI 3.95 to 9.14). A significant drop in viral load was observed while new emerging variants of the hypervariable region 1 of HCV replaced the predominant variants present before therapy, particularly in those patients with a more prominent drop in viral load. This antiviral effect was associated with an enhanced specific anti-HCV immune response.
Tremelimumab safety profile and antitumor and antiviral activity in patients with advanced HCC developed on HCV-induced liver cirrhosis support further investigation.
CITATION J Hepatol. 2013 Mar 2. pii: S0168-8278(13)00144-X. doi: 10.1016/j.jhep.2013.02.022
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