{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T04:27:21Z","timestamp":1783225641657,"version":"3.54.6"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Uveal melanoma is a common intraocular malignant tumor that is uniformly fatal once metastatic. No effective adjuvant therapy currently exists to reduce the risk of distant metastasis after definitive treatment of the primary lesion. Immunotherapy has been used effectively in the adjuvant setting in locally advanced cutaneous melanoma. We performed a Phase I\/II clinical trial of adjuvant ipilimumab in high-risk primary uveal melanoma with distant metastasis-free survival (DMFS) as the primary objective. A total of 10 patients with genomically high-risk disease were treated: three at a dose of 3 mg\/kg and seven at 10 mg\/kg. Two of the seven patients at the higher dose had to discontinue therapy secondary to grade 3 toxicity. At 36 months follow-up, 80% of patients had no evidence of distant disease (95% CI, 58.7\u2013100). With recent advancements in CTLA-4 inhibition, PD-1 inhibition, and combined checkpoint blockade, immunotherapy is a promising avenue of treatment in uveal melanoma. Further clinical trials are needed to elucidate the role of immunotherapy in the adjuvant setting.<\/jats:p>","DOI":"10.3390\/cancers11020152","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T11:27:52Z","timestamp":1548761272000},"page":"152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Adjuvant Ipilimumab in High-Risk Uveal Melanoma"],"prefix":"10.3390","volume":"11","author":[{"given":"Eric","family":"Fountain","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland L.","family":"Bassett","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Cain","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liberty","family":"Posada","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2867-6320","authenticated-orcid":false,"given":"Dan S.","family":"Gombos","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Section of Ophthalmology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hwu","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agop","family":"Bedikian","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1339-1517","authenticated-orcid":false,"given":"Sapna P.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S0161-6420(03)00078-2","article-title":"Incidence of uveal melanoma in the United States: 1973\u20131997","volume":"110","author":"Singh","year":"2003","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.ophtha.2011.01.040","article-title":"Uveal melanoma: Trends in incidence, treatment, and survival","volume":"118","author":"Singh","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1002\/cncr.29727","article-title":"Uveal melanoma: From diagnosis to treatment and the science in between","volume":"122","author":"Chattopadhyay","year":"2016","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1586\/14737140.6.4.493","article-title":"Treatment of primary intraocular melanoma","volume":"6","author":"Damato","year":"2006","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4651","DOI":"10.1167\/iovs.03-0538","article-title":"Very long-term prognosis of patients with malignant uveal melanoma","volume":"44","author":"Kujala","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ajo.2009.01.023","article-title":"Effectiveness of treatments for metastatic uveal melanoma","volume":"148","author":"Augsburger","year":"2009","journal-title":"Am. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s11912-008-0066-z","article-title":"The biology and management of uveal melanoma","volume":"10","author":"Sato","year":"2008","journal-title":"Curr. Oncol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ohc.2004.07.003","article-title":"Metastatic uveal melanoma","volume":"18","author":"Singh","year":"2005","journal-title":"Ophthalmol. Clin. N. Am."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3109\/08820538.2016.1154175","article-title":"Tumor Characteristics, Genetics, Management, and the Risk of Metastasis in Uveal Melanoma","volume":"31","author":"Nichols","year":"2016","journal-title":"Semin. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1167\/iovs.16-20212","article-title":"The Prognostic Value of AJCC Staging in Uveal Melanoma Is Enhanced by Adding Chromosome 3 and 8q Status","volume":"58","author":"Dogrusoz","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.ophtha.2012.02.017","article-title":"Collaborative Ocular Oncology Group report number 1: Prospective validation of a multi-gene prognostic assay in uveal melanoma","volume":"119","author":"Onken","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1001\/archophthalmol.2009.208","article-title":"Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes","volume":"127","author":"Shields","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/(SICI)1098-2264(199705)19:1<22::AID-GCC4>3.0.CO;2-2","article-title":"Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis","volume":"19","author":"Sisley","year":"1997","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.1167\/iovs.11-8697","article-title":"Higher percentage of FISH-determined monosomy 3 and 8q amplification in uveal melanoma cells relate to poor patient prognosis","volume":"53","author":"Vaarwater","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1016\/j.ophtha.2009.04.044","article-title":"Adjuvant interferon therapy for patients with uveal melanoma at high risk of metastasis","volume":"116","author":"Lane","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S0002-9394(14)77876-6","article-title":"A randomized study of methanol-extraction residue of bacille Calmette-Guerin as postsurgical adjuvant therapy of uveal melanoma","volume":"110","author":"McLean","year":"1990","journal-title":"Am. J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Valsecchi, M.E., Orloff, M., Sato, R., Chervoneva, I., Shields, C.L., Shields, J.A., Mastrangelo, M.J., and Sato, T. (2017). Adjuvant Sunitinib in High-Risk Patients with Uveal Melanoma: Comparison with Institutional Controls. Ophthalmology.","DOI":"10.1016\/j.ophtha.2017.08.017"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/CMR.0b013e32830317de","article-title":"Adjuvant intra-arterial hepatic fotemustine for high-risk uveal melanoma patients","volume":"18","author":"Voelter","year":"2008","journal-title":"Melanoma Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chan, P.Y., Hall, P., Hay, G., Cohen, V.M.L., and Szlosarek, P.W. (2017). A major responder to ipilimumab and nivolumab in metastatic uveal melanoma with concomitant autoimmunity. Pigment Cell Melanoma Res.","DOI":"10.1111\/pcmr.12607"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00262-011-1089-0","article-title":"Ipilimumab in pretreated patients with metastatic uveal melanoma: Safety and clinical efficacy","volume":"61","author":"Danielli","year":"2012","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e1143997","DOI":"10.1080\/2162402X.2016.1143997","article-title":"Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma","volume":"5","author":"Karydis","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.3109\/0284186X.2013.786839","article-title":"Ipilimumab in pretreated metastastic uveal melanoma patients. Results of the Dutch Working group on Immunotherapy of Oncology (WIN-O)","volume":"52","author":"Kelderman","year":"2013","journal-title":"Acta Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/CMR.0b013e32835b554f","article-title":"Ipilimumab activity in advanced uveal melanoma","volume":"23","author":"Khattak","year":"2013","journal-title":"Melanoma Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/CMR.0000000000000242","article-title":"The use of pembrolizumab for the treatment of metastatic uveal melanoma","volume":"26","author":"Kottschade","year":"2016","journal-title":"Melanoma Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1002\/cncr.28282","article-title":"Clinical activity of ipilimumab for metastatic uveal melanoma: A retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience","volume":"119","author":"Luke","year":"2013","journal-title":"Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1093\/annonc\/mdt376","article-title":"Efficacy and safety of ipilimumab in patients with pre-treated, uveal melanoma","volume":"24","author":"Maio","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zimmer, L., Vaubel, J., Mohr, P., Hauschild, A., Utikal, J., Simon, J., Garbe, C., Herbst, R., Enk, A., and Kampgen, E. (2015). Phase II DeCOG-study of ipilimumab in pretreated and treatment-naive patients with metastatic uveal melanoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118564"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S1470-2045(15)70122-1","article-title":"Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): A randomised, double-blind, phase 3 trial","volume":"16","author":"Eggermont","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_29","first-page":"399","article-title":"Ipilimumab Adjuvant Therapy in Melanoma","volume":"376","author":"Eggermont","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1056\/NEJMoa1709030","article-title":"Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma","volume":"377","author":"Weber","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7205","DOI":"10.1158\/0008-5472.CAN-04-1750","article-title":"Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death","volume":"64","author":"Onken","year":"2004","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Correa, Z.M., and Augsburger, J.J. (2016). Independent Prognostic Significance of Gene Expression Profile Class and Largest Basal Diameter of Posterior Uveal Melanomas. Am. J. Ophthalmol., 162.","DOI":"10.1016\/j.ajo.2015.11.019"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1001\/jamaophthalmol.2016.0913","article-title":"Prognostic Implications of Tumor Diameter in Association with Gene Expression Profile for Uveal Melanoma","volume":"134","author":"Walter","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1056\/NEJMoa1104621","article-title":"Ipilimumab plus dacarbazine for previously untreated metastatic melanoma","volume":"364","author":"Robert","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus Ipilimumab in Advanced Melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1097\/CMR.0000000000000175","article-title":"A phase 2 study of tremelimumab in patients with advanced uveal melanoma","volume":"25","author":"Joshua","year":"2015","journal-title":"Melanoma Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","article-title":"Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma","volume":"377","author":"Wolchok","year":"2017","journal-title":"N. Engl. J. 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