title: Ipilimumab: unleashing the power of the immune system through CTLA-4 blockade.
abstract: Malignant melanoma is rising faster in incidence than any other malignancy. Long-term remission or "cure" is rare and is almost exclusively limited to therapies that stimulate an immune antitumor response. Ipilimumab is a novel targeted human immunostimulatory monoclonal antibody that blocks cytotoxic T-lymphocyte antigen4 (CTLA-4), an immune-inhibitory site expressed on activated T cells. Ipilimumab is well tolerated as an outpatient infusion therapy. Multiple studies have confirmed significant antimelanoma activity. A randomized trial has documented a survival benefit when ipilimumab was compared to a gp-100 vaccine only arm. The unique mechanism of action of ipilimumab makes assessment of response by conventional criteria difficult. Benefit from ipilimumab can occur after what would be considered progression with World Health Oganization (WHO) or Response Evaluation Criteria in Solid Tumors (RECIST) criteria. New immune response criteria have been proposed. Therapeutic responses peak between 12 and 24 weeks, with slow responses continuing up to and beyond 12 months. The major drug- related adverse side effects (10%-15% grade 3 or above) are immune-related and consist most commonly of rash, colitis, hypophysitis, thyroiditis, and hepatitis. Colonic perforation can occur and patients with diarrhea have to be monitored carefully with strict adherence to treatment algorithms. Algorithms for the treatment of other adverse side effects have been developed. The treatment of immune-related side effects with immunosuppressive agents, such as corticosteroids, does not appear to impair antitumor response. With proper monitoring and management of side effects, ipilimumab is an extremely safe drug to administer. The benefits of ipilimumab will most certainly extend to other malignancies in the near future.
authors.affiliation: The Angeles Clinic & Research Institute, 2001 Santa Monica Blvd, Suite 560W, Santa Monica, CA 90404, USA. pboasberg@theangelesclinic.org
authors.forename: Peter
authors.initials: P
authors.lastname: Boasberg
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.forename: Steven
authors.initials: S
authors.lastname: O'Day
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D060908:CTLA-4 Antigen; D003606:Dacarbazine / Q000008:administration & dosage; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab; D003606:Dacarbazine