Melanoma remains a critical public health problem worldwide. Patients with stage IV disease have very poor prognosis and their 1-year survival rate is only 25%. Until recently, systemic treatments with a positive impact on overall survival (OS) had remained elusive. In recent years, the United States Food and Drug Administration (FDA) - approved several novel agents targeting the RAS/RAF/MEK/ERK pathway (
vemurafenib,
dabrafenib, and
trametinib) - critical in cell division and proliferation of
melanoma, and an
immune checkpoint inhibitor (
ipilimumab) directed against the cytotoxic T lymphocyte
Antigen - (CTLA-4). Moreover, recent reports of clinical trials studying other immune checkpoint modulating agents will most likely result in their FDA approval within the next months. This review focuses on
ipilimumab, its safety and efficacy, and future considerations.
Ipilimumab has demonstrated a positive OS impact after a several-year follow-up. It is also recognized that due to its mechanism of action, the response patterns to
ipilimumab can differ from those observed in patients following treatment with conventional
cytotoxic agents and even the most recently approved BRAF inhibitors. Most patients (84.8%) experience
drug-related adverse events (AEs) of any grade; most of these are mild to moderate and immune mediated. However, a minority of patients may also experience severe and life-threatening AEs. In clinical studies, AEs were managed according to guidelines that emphasized close clinical monitoring and early use of
corticosteroids when appropriate. Preliminary results have taught us the potential greater toxicity when in combination with
vemurafenib, and the greater antitumor efficacy when combined with
nivolumab, a
monoclonal antibody directed against programmed death receptor-1 (PD-1), another
immune checkpoint inhibitor. Future challenges include the optimization of dosing and toxicities when used as a single agent, and studying the safety and efficacy of combinations with targeted small molecules and other
monoclonal antibodies to treat patients with
melanoma and other
malignancies.