Ipilimumab efficacy and safety in patients with advanced melanoma: a retrospective analysis of HLA subtype from four trials

Jedd D. Wolchok1, Jeffrey S. Weber2, Omid Hamid3, Celeste Lebbé4, Michele Maio5, Dirk Schadendorf6, Veerle de Pril7, Kevin Heller8, Tai-Tsang Chen9, Ramy Ibrahim9, Axel Hoos9 and Steven J. O'Day3

1Memorial Sloan-Kettering Cancer Center, New York, USA

2H. Lee Moffitt Cancer Center, Tampa, FL, USA

3The Angeles Clinic and Research Institute, Santa Monica, CA, USA

4AP-HP, Hôpital Saint-Louis, Service de Dermatologie; Université Paris Diderot Paris7, INSERM U976 Skin Research Center, Paris, France

5University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy

6University Hospital Essen, Essen, Germany

7Bristol-Myers Squibb, Braine-l'Alleud, Belgium

8Bristol-Myers Squibb, Plainsboro, NJ, USA

9Bristol-Myers Squibb, Wallingford, CT, USA

Communicated by: LJ Old

Keywords: clinical trial, melanoma, ipilimumab, HLA, treatment outcome


Ipilimumab is a fully human, monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor T-cell response. This agent improved overall survival in a phase III trial in previously treated patients with advanced melanoma. Because the mechanism of action for ipilimumab is thought to be HLA independent, most trials enrolled patients without regard to HLA subtype. However, enrollment in the phase III trial was restricted to class-I HLA-A*0201-positive patients because two of the three arms contained an HLA-A*0201-restricted gp100 vaccine. HLA typing was also performed prospectively in several phase II trials and was available for 93.5% of patients. In this retrospective analysis, pooled efficacy and safety data are presented according to HLA-A*0201 status and dose from pretreated patients randomized to 0.3, 3, or 10 mg/kg ipilimumab in four phase II trials. Median overall survival (OS) was similar for the 187 HLA-A*0201-positive [9.3 months, 95% CI (confidence interval) 7.4-11.5] and 266 HLA-A*0201-negative patients [11.4 months, 95% CI 9.3-15.1] randomized to ipilimumab at all doses across the four phase II trials. These data are comparable to the OS for the 137 HLA-A*0201-positive patients randomized to ipilimumab in the phase III study [10.1 months, 95% CI 8.0-13.8]. Ipilimumab-induced adverse events and immune-related adverse events (skin, gastrointestinal, hepatic, other) also occurred at similar frequencies among patients in the phase II and III trials, regardless of HLA-A*0201 status. These findings support the hypothesis that ipilimumab-treated patients with advanced melanoma have similar outcomes regardless of their HLA-A*0201 status.