{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:37:16Z","timestamp":1790883436896,"version":"4.1.0"},"reference-count":47,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"unspecified","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Link"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,5,26]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>CheckMate 915 (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03068455\">NCT03068455<\/jats:ext-link>) compared adjuvant nivolumab monotherapy versus combination nivolumab+ipilimumab in patients with resected stage III\/IV melanoma. This exploratory analysis was performed to identify biomarkers that correlate with benefit from adjuvant immunotherapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and methods<\/jats:title>\n                  <jats:p>1,844 patients received nivolumab 480\u2009mg every 4 weeks or nivolumab 240\u2009mg every 2 weeks with ipilimumab 1\u2009mg\/kg every 6 weeks. Tumor and peripheral biomarkers were evaluated, including tumor-informed circulating tumor DNA (ctDNA) at postresection baseline and on-treatment, for their association with recurrence-free survival and distant metastases-free survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Biomarker analyses were conducted in 60\u201396% of the intention-to-treat population. ctDNA positivity at baseline (seen in 16.2% of patients) and on-treatment was associated with higher risk of recurrence than ctDNA negativity (HR, 1.97; 95%\u2009CI, 1.57 to 2.46), with a high specificity (87%) and modest sensitivity (39%). ctDNA status, tumor mutational burden (TMB) status (TMB &lt; or \u2265350 mutations\/tumor) and interferon gamma-RNA signature score (&lt; or \u2265median) evaluated together, as well as ctDNA status with tumor CD8 or cell programmed death ligand 1 expression, were more predictive of survival than ctDNA alone. Tumor bulk RNA-seq expression patterns identified gene expression at baseline associated with recurrence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study represents the largest assessment of ctDNA and other baseline tumor and peripheral biomarkers for predicting recurrence-free survival in patients with resected melanoma receiving adjuvant immunotherapy. ctDNA alone and in combination with more established biomarkers predicted recurrence-free and distant metastasis-free survival and has potential utility for assessing and monitoring the risk of recurrence in patients with resected melanoma treated with immunotherapy in the adjuvant setting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03068455\">NCT03068455<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2025-012034","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T13:55:18Z","timestamp":1752242118000},"page":"e012034","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Pretreatment and on-treatment ctDNA and tissue biomarkers predict recurrence in patients with stage IIIB\u2013D\/IV melanoma treated with adjuvant immunotherapy: CheckMate 915"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03068455","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03068455","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03068455","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Georgina 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