title: Do human lymphocyte antigens play a role in the clinical antimelanoma activity of ipilimumab?
abstract: Evaluation of: Wolchok JD, Weber JS, Hamid O et al.: Ipilimumab efficacy and safety in patients with advanced melanoma: a retrospective analysis of HLA subtype from four trials. Cancer Immun. 10, 9-14 (2010). For the first time, a pivotal Phase III clinical trial has demonstrated an overall survival benefit for an antimelanoma drug, ipilimumab, in previously treated advanced melanoma patients. Ipilimumab is a T-cell-potentiating monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4. All patients in this study were HLA-A2*0201 positive because the active control arm contained a HLA-A2*0201-restricted peptide derived from the melanocyte differentiation antigen, gp100. Hence, the following question arises: does the survival benefit conferred by ipilimumab treatment only benefit HLA-A2*0201-positive melanoma patients? However, the current paper reveals a retrospective analysis to show that advanced melanoma patients obtain a survival benefit from ipilimumab irrespective of HLA-A2*0201 status. This analysis also raises other interesting questions regarding the HLA dependence of mechanisms underlying the toxicity and antimelanoma activity of ipilimumab, which are discussed.
authors.affiliation: Cancer Clinical Trials Unit, Royal Adelaide Hospital Cancer Centre, Adelaide, SA, Australia. michael.brown@health.sa.gov.au
authors.forename: Michael P
authors.initials: MP
authors.lastname: Brown