{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:41:29Z","timestamp":1784864489950,"version":"3.55.0"},"reference-count":22,"publisher":"Harborside Press, LLC","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2]]},"abstract":"Background:<\/jats:bold> Uveal melanoma (UM) is an uncommon melanoma subtype with poor prognosis. Agents that have transformed the management of cutaneous melanoma have made minimal inroads in UM. Methods:<\/jats:bold> We conducted a single-arm phase II study of pembrolizumab in patients with metastatic UM and performed bioinformatics analyses of publicly available datasets to characterize the activity of anti\u2013PD-1 in this setting and to understand the mutational and immunologic profile of this disease. Results:<\/jats:bold> A total of 5 patients received pembrolizumab in this study. Median overall survival was not reached, and median progression-free survival was 11.0 months. One patient experienced a complete response after one dose and 2 others experienced prolonged stable disease (20% response rate, 60% clinical benefit rate); 2 additional patients had rapidly progressing disease. Notably, the patients who benefited had either no liver metastases or small-volume disease, whereas patients with rapidly progressing disease had bulky liver involvement. We performed a bioinformatics analysis of The Cancer Genome Atlas for UM and confirmed a low mutation burden and low rates of T-cell inflammation. Note that the lack of T-cell inflammation strongly correlated with MYC<\/jats:italic> pathway overexpression. Conclusions:<\/jats:bold> Anti\u2013PD-1\u2013based therapy may cause clinical benefit in metastatic UM, seemingly more often in patients without bulky liver metastases. Lack of mutation burden and T-cell infiltration and MYC<\/jats:italic> overexpression may be factors limiting therapeutic responses.<\/jats:p>ClinicalTrials.gov<\/jats:ext-link> identifier:<\/jats:bold> NCT02359851<\/jats:p>","DOI":"10.6004\/jnccn.2018.7070","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T20:25:53Z","timestamp":1550694353000},"page":"114-117","source":"Crossref","is-referenced-by-count":63,"title":["Response to Anti\u2013PD-1 in Uveal Melanoma Without High-Volume Liver Metastasis"],"prefix":"10.6004","volume":"17","author":[{"given":"Douglas B.","family":"Johnson","sequence":"first","affiliation":[{"name":"aDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riyue","family":"Bao","sequence":"additional","affiliation":[{"name":"bDepartment of Medicine, University of Chicago, Chicago, Illinois;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin K.","family":"Ancell","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony B.","family":"Daniels","sequence":"additional","affiliation":[{"name":"cDepartment of Ophthalmology, Vanderbilt University Medical Center, Nashville, Tennessee; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Wallace","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Sosman","sequence":"additional","affiliation":[{"name":"dDepartment of Medicine, Robert H. Lurie Cancer Center and Northwestern University, Chicago, Illinois."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason J.","family":"Luke","sequence":"additional","affiliation":[{"name":"bDepartment of Medicine, University of Chicago, Chicago, Illinois;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"ref101","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrc.2017.117","article-title":"Impact of oncogenic pathways on evasion of antitumour immune responses","volume":"18","author":"Spranger","year":"2018","journal-title":"Nat Rev Cancer"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature14404","article-title":"Melanoma-intrinsic \u03b2-catenin signalling prevents anti-tumour immunity","volume":"523","author":"Spranger","year":"2015","journal-title":"Nature"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1002\/cncr.30258","article-title":"Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies","volume":"122","author":"Algazi","year":"2016","journal-title":"Cancer"},{"key":"ref161","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":"ref241","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1158\/2326-6066.CIR-16-0325","article-title":"Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC","volume":"5","author":"Tumeh","year":"2017","journal-title":"Cancer Immunol Res"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.cell.2017.10.022","article-title":"Epigenetic therapy ties MYC depletion to reversing immune evasion and treating lung cancer","volume":"171","author":"Topper","year":"2017","journal-title":"Cell"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ccell.2017.07.003","article-title":". 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