Ipilimumab: an Anti-CTLA-4 Antibody for Metastatic Melanoma
Cet article passe en revue les travaux récents sur l'ipilimumab pour le traitement du mélanome métastatique
Ipilimumab (MDX-010, Yervoy ®), a fully human monoclonal antibody against Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), was recently approved by the U.S. Food and Drug Administration for the treatment of metastatic melanoma. In both early and late phase trials, Ipilimumab has demonstrated consistent activity against melanoma. For example, in a randomized phase III trial that enrolled patients with previously treated, metastatic disease, ipilimumab, with or without a peptide vaccine, improved overall survival (OS): median OS was 10.1 and 10.0 months in the ipilimumab and ipilimumab plus vaccine arms respectively, versus 6.4 months in the vaccine alone group. (hazard ratio 0.68, p≤0.003) Serious (grade 3 - 5) immune related adverse events occurred in 10-15% of patients. Thus, while providing a clear survival benefit, ipilimumab administration requires careful patient monitoring and sometimes necessitates treatment with immune-suppressive therapy. Here, we review the mechanism of action, preclinical data and multiple clinical trials which led to the FDA's approval of ipilimumab for metastatic melanoma.