Checkpoint modulation in melanoma: an update on ipilimumab and future directions.
Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody, was the first therapy demonstrated to improve overall survival in melanoma. Since ipilimumab's approval by the FDA in 2011, a wealth of data has amassed, helping clinicians to optimize its use. We have learned how to mitigate the adverse effects of ipilimumab, identified its effects in melanoma subpopulations such as those with brain metastases, uveal melanoma, and mucosal melanoma, discovered potential biomarkers of activity, and investigated its use in combination with other therapeutic modalities. These discoveries have paved the way for rapid development of second-generation immunomodulatory antibodies such as inhibitors of the programmed cell death 1 receptor axis. These new agents hold promise as monotherapy, but perhaps the greatest allure lies in the possibility of combining these agents in synergistic multidrug regimens.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA, paged@mskcc.org.
David B
DB
Page
Michael A
MA
Postow
Margaret K
MK
Callahan
Jedd D
JD
Wolchok
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor