The ipilimumab lesson in melanoma: Achieving long-term survival

The anti-cytotoxic T-lymphocyte antigen-4 (anti CTLA-4) antibody ipilimumab is the first treatment that significantly improved the survival rates of metastatic melanoma patients, marking a new era in the treatment of melanoma. During its development, a hallmark of ipilimumab therapy was the extended duration of response, achieved in 20% of patients. The follow-up of patients included in phase II and phase III trials and in expanded access programs revealed that the survival rates remained stable after 3 years. These results demonstrated that ipilimumab induces an effective anti-tumor immune response persisting after the completion of treatment, and suggested a potential remission in a subset of patients. In this article we review the development of ipilimumab and highlight the long-term results. This approach emphasizes the need to optimize the use of ipilimumab in the future, by identifying the patients most likely to achieve long term survival after ipilimumab therapy, and by developing combined therapeutic approaches involving cytotoxic agents, targeted therapies or other immunotherapies to achieve durable control in a larger proportion of patients. (C) 2015 Elsevier Inc. All rights reserved.