Ipilimumab efficacy and safety in patients with advanced melanoma: a retrospective analysis of HLA subtype from four trials.
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.
Memorial Sloan-Kettering Cancer Center, New York 10021 , USA. wolchokj@mskcc.org
Jedd D
JD
Wolchok
Jeffrey S
JS
Weber
Omid
O
Hamid
Celeste
C
Lebbé
Michele
M
Maio
Dirk
D
Schadendorf
Veerle
V
de Pril
Kevin
K
Heller
Tai-Tsang
TT
Chen
Ramy
R
Ibrahim
Axel
A
Hoos
Steven J
SJ
O'Day
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D000074324:Ipilimumab