Ipilimumab is directed against an antigen on the surface of T cells. The antigen, cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), acts as a brake on the T cell diminshes T-cell activity.
Ipilimumab was first described to large audiences in the August 19 issue of the New England Journal of Medicine after being first presented at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting. In the study, patients receiving ipilimumab plus a peptide vaccine (glycoprotein 100) had a median survival of 10 months, compared with 6.4 months for patients receiving the vaccine alone (P < .001). Patients were assigned to one of three treatment groups: 1) ipilimumab; 2) ipilimumab plus the gp100 vaccine; or 3) the gp100 vaccine alone. The gp100 vaccine is an experimental melanoma vaccine that is also designed to stimulate T cells to attack melanoma cells. In previous studies it has shown modest anticancer activity and was superior to treatment with IL-2.
•Median overall survival was 10 months in the groups that received ipilimumab, compared with 6.5 months in the group that received the gp100 vaccine alone.
•Two-year survival was 24% among patients who received ipilimumab alone, 22% among those who received ipilimumab and the gp100 vaccine, and 14% among those who received the gp100 vaccine alone.
•Six-month progression-free survival was 30% among patients in the ipilimumab groups and 11% among patients in the group that received the gp100 vaccine alone.
•Ipilimumab was generally well tolerated, but 10-14% of patients treated with ipilimumab experienced sometimes severe side effects such as rash and colitis (inflammation of the colon). The frequency among patients treated with gp100 was roughly 3%. All of the study participants had undergone previous treatment for the disease.
On March 25, 2011, the US Food and Drug Administration (FDA) approved ipilimumab for the treatment of unresectable or metastatic melanoma. Due to potentially severe or even fatal safety issues, the FDA approved this agent with a Risk Evaluation and Mitigation Strategy (REMS) to ensure the benefits of the agent outweigh the risks, although this requirement was later suspended.
YERVOY (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma.
NCCN included it as category 1.
Hwu P. A phase III, randomized, double-blind, multicenter study comparing monotherapy with ipilimumab or gp100 N Engl J Med 2010; 363:779 – 781
O’Day S, Hodi FS, McDermott DF et al. A phase III, randomized, double-blind, multicenter study comparing monotherapy with ipilimumab or gp100 peptide vaccine and the combination in patients with previously treated, unresectable stage III or IV melanoma. Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract 4.