Ipilimumab. Immunostimulant; more assessment needed.

ABSTRACT

In patients with inoperable or metastatic melanoma, first-line cytotoxic drugs have no proven impact on survival, which is generally limited to only a few months. There is no standard second-line treatment. Ipilimumab, a monoclonal antibody, stimulates T lymphocyte proliferation and activation. It has been authorised in the European Union for melanoma patients in whom one or more lines of chemotherapy have failed. Clinical evaluation is based on a double-blind randomised trial in 676 patients comparing ipilimumab + gp 100, ipilimumab + placebo, and 100 gp + placebo. Gp 100 is an experimental mixture of proteins being tested in melanoma. The median overall survival time was significantly longer among patients treated with ipilimumab, with or without gp 100 (about 10 months), than among those receiving gp 100 + placebo (about 6 months). In another trial, involving previously untreated melanoma patients, adding ipilimumab (at a dose 3 times higher than in the previous trial) to dacarbazine prolonged median overall survival by 2 months. The main adverse effects of ipilimumab are immune-related adverse reactions, and include gastrointestinal, cutaneous and endocrine disorders (enterocolitis with or without perforation, dermatitis, hypopituitarism and hepatitis). In practice, in patients with metastatic melanoma in whom one or more treatments have failed, the use of ipilimumab should be restricted to well-designed clinical trials designed to better assess the survival benefit, serious adverse effects, and the optimal dosage.