Ipilimumab for advanced melanoma: a pharmacologic perspective

Ipilimumab, a fully human anti-CTLA-4 antibody, has been approved for the treatment of unresectable or metastatic melanoma based on its survival benefit demonstrated in randomized phase III studies. The current approved dosing schedule of ipilimumab is 3 mg/kg as a 90-min intravenous infusion every 3 weeks for a total of 4 doses. The immune-mediated mechanism of action of ipilimumab can result in tumor response patterns that may differ from those observed with conventional chemotherapy; therefore, revised response criteria to fully capture the spectrum of responses have been developed and are being prospectively validated. The safety profile of ipilimumab also reflects its mechanism of action and is characterized by immune-related adverse events. Although most of these events are mild, tolerable and reversible, high-grade immune-related adverse events have been observed in 15% of patients and can be potentially life-threatening if not managed appropriately. Guidelines for the management of these events emphasize thorough patient education, vigilant monitoring and prompt intervention with corticosteroids when appropriate. Ongoing research, including evaluation of ipilimumab in the adjuvant setting, investigation of its use in combination with other agents and assessment of alternative doses, will help optimize and expand the use of this innovative treatment.