Ipilimumab: report and comment about the MDX010-020 clinical trial

Ipilimumab is a human monoclonal antibody, that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), normally expressed in activated T cells. CTLA-4 downregulates T-cell activation pathways and induces progressive immune tolerance. Blocking this downregulation, determines an enhancement of antitumor T-lymphocyte response. A recent randomized Phase III trial using ipilimumab (MDX020-010) demonstrated, for the first time, a statistically significant improvement in overall survival in patients with metastatic melanoma, prolonging median survival from 6.4 to 10.1 months. It is noteworthy that the study population was composed of previously treated patients, of whom more than 70% had poor prognostic factors and that the adverse events experienced were reversed with appropriate treatment. Further trials are now needed to evaluate the real impact of ipilimumab on survival and on response duration in treatment-naive patients. Clinical research is also warranted into the association of ipilimumab with chemoimmunother...