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Until recently, systemic treatments with a positive impact on overall survival (\n                    <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>\n                    ) had remained elusive. In recent years, the United States Food and Drug Administration (FDA) \u2013 approved several novel agents targeting the RAS\/RAF\/MEK\/ERK pathway (vemurafenib, dabrafenib, and trametinib) \u2013 critical in cell division and proliferation of melanoma, and an immune checkpoint inhibitor (ipilimumab) directed against the cytotoxic T lymphocyte Antigen \u2010 (CTLA\u20104). Moreover, recent reports of clinical trials studying other immune checkpoint modulating agents will most likely result in their\n                    <jats:styled-content style=\"fixed-case\">FDA<\/jats:styled-content>\n                    approval within the next months. This review focuses on ipilimumab, its safety and efficacy, and future considerations. Ipilimumab has demonstrated a positive\n                    <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>\n                    impact after a several\u2010year follow\u2010up. 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\n                    <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content>\n                    inhibitors. Most patients (84.8%) experience drug\u2010related adverse events (\n                    <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\n                    s) of any grade; most of these are mild to moderate and immune mediated. However, a minority of patients may also experience severe and life\u2010threatening\n                    <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\n                    s. In clinical studies,\n                    <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\n                    s 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\u20101 (\n                    <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                    \u20101), 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.\n                  <\/jats:p>","DOI":"10.1002\/cam4.371","type":"journal-article","created":{"date-parts":[[2015,1,25]],"date-time":"2015-01-25T00:23:33Z","timestamp":1422145413000},"page":"661-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":126,"title":["<scp>CTLA<\/scp>\n                    \u20104 blockade with ipilimumab: biology, safety, efficacy, and future considerations"],"prefix":"10.1002","volume":"4","author":[{"given":"Luis H.","family":"Camacho","sequence":"first","affiliation":[{"name":"St. Luke's Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21208"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.9.678"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.7837"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00766"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60868-X"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203421"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1210093"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","DOI":"10.1200\/jco.2011.29.15_suppl.8597","article-title":"Frequency of mutations associated with targeted therapy in malignant melanoma patients","volume":"29","author":"Cheng S.","year":"2011","journal-title":"J. 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