Ipilimumab in the treatment of metastatic melanoma: management of adverse events

Abstract

Giuseppina Della Vittoria Scarpati,1,2 Celeste Fusciello,3 Francesco Perri,4 Francesco Sabbatino,5 Soldano Ferrone,5 Chiara Carlomagno,3 Stefano Pepe1,2 1Department of Medicine, University of Salerno, 2Division of Oncology, “San Giovanni di Dio e Ruggi d’Aragona” Hospital, Salerno, 3Department of Oncology, University “Federico II”, Naples, 4Head and Neck Medical Oncology Unit, National Tumor Institute, Naples, Italy; 5Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Abstract: Recently, “ipilimumab,” an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, has been demonstrated to improve overall survival in metastatic melanoma. “CTLA-4” is an immune-checkpoint molecule that downregulates pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove the CTLA-4 inhibitory signal, allowing the immune system to react to cancer cells. Due to its immune-based mechanism of action, ipilimumab causes the inhibition of CTLA-4-mediated immunomodulatory effects, the enhancement of antitumor specific immune response mediated by the weakening of self-tolerance mechanisms while exacerbating the development of autoimmune diseases and immune-related adverse events, including dermatitis, hepatitis, enterocolitis, hypophysitis, and uveitis. Keywords: melanoma, T-cells, CTLA-4, autoimmunity, adverse events