{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:09:23Z","timestamp":1779379763238,"version":"3.53.1"},"reference-count":20,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"unspecified","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,8,11]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Treatment-free survival (TFS; time spent free of systemic anticancer therapy) is increasingly used to support traditional endpoints. TFS was previously evaluated in patients with advanced melanoma treated with nivolumab plus ipilimumab. This analysis compared TFS for nivolumab plus relatlimab and nivolumab monotherapy in patients with advanced melanoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data were from 714 patients in the phase 2\/3 RELATIVITY-047 trial (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03470922\">NCT03470922<\/jats:ext-link>\n                      ). TFS was defined as the difference in restricted mean event times between the Kaplan-Meier curves for time to protocol therapy cessation and time to subsequent systemic anticancer therapy initiation or death. TFS was further partitioned into time with and time without grade \u22653 treatment-related adverse events (TRAEs). Subgroup analysis based on tumor\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutational status and tumor programmed death ligand 1 (PD-L1) expression level was conducted. Between-treatment group differences were calculated with bootstrapped 95% CIs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At 48 months from randomization, Kaplan-Meier estimates of overall survival were 52% and 43% for patients in the nivolumab plus relatlimab and nivolumab groups, respectively; 38% and 33% of patients in these respective groups were free of subsequent systemic therapy. The 48-month mean TFS was 2.9 months (95%\u2009CI 1.0 to 4.9) longer with nivolumab plus relatlimab than with nivolumab (9.7 vs 6.8 months, respectively). Mean TFS represented 20% and 14% of the 48-month period after initiating nivolumab plus relatlimab and nivolumab, respectively. Considering only time without grade \u22653 TRAEs, the 48-month mean TFS was 2.6 months (95%\u2009CI 0.8 to 4.5) longer with nivolumab plus relatlimab than with nivolumab (9.1 vs 6.5 months, respectively). The 48-month mean total TFS was consistently longer with nivolumab plus relatlimab than with nivolumab in the\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutant (9.4 vs 6.5 months),\n                      <jats:italic>BRAF<\/jats:italic>\n                      wild-type (9.9 vs 6.9 months), PD-L1 \u22651% (12.3 vs 7.7 months), and PD-L1&lt;1% (7.9 vs 6.2 months) subgroups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This analysis demonstrated TFS benefit during the 48 months since initiating nivolumab plus relatlimab compared with nivolumab alone in patients with advanced melanoma. A direct comparison between nivolumab plus relatlimab and nivolumab plus ipilimumab is needed to determine the differences between the regimens in TFS and those in traditional endpoints.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012747","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T11:10:27Z","timestamp":1757675427000},"page":"e012747","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Analysis of treatment-free survival of patients with advanced melanoma receiving nivolumab as monotherapy or in combination with relatlimab in RELATIVITY-047"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03470922","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03470922","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2428-6109","authenticated-orcid":false,"given":"Meredith M","family":"Regan","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"suffix":"MD","given":"Paolo A","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Istituto Nazionale dei Tumori IRCCS \u201cFondazione G. Pascale\u201d, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2976-0911","authenticated-orcid":false,"given":"Evan J","family":"Lipson","sequence":"additional","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennell","family":"Palaia","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriy","family":"Moshyk","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Selvan","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D","family":"Lao","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-9924","authenticated-orcid":false,"suffix":"MD","given":"Michael B","family":"Atkins","sequence":"additional","affiliation":[{"name":"Georgetown University Lombardi Comprehensive Cancer Center, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2675-5095","authenticated-orcid":false,"given":"David F","family":"McDermott","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Potluri","sequence":"additional","affiliation":[{"name":"Putnam Associates, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandip","family":"Ranjan","sequence":"additional","affiliation":[{"name":"Putnam Associates, Gurugram, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Bilthare","sequence":"additional","affiliation":[{"name":"Putnam Associates, Gurugram, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8894-3545","authenticated-orcid":false,"given":"Georgina V","family":"Long","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Stephen Hodi","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1942-851X","authenticated-orcid":false,"given":"Hussein","family":"Tawbi","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-7858","authenticated-orcid":false,"given":"Dirk","family":"Schadendorf","sequence":"additional","affiliation":[{"name":"University of Essen and the German Cancer Consortium, Essen, Germany; National Center for Tumor Diseases, Essen, Germany; and University Alliance Ruhr, University Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"2026052108452062000_13.9.e012747.1","first-page":"418","article-title":"Immune checkpoint blockade: a new paradigm in treating advanced cancer","volume":"5","author":"Kreamer","year":"2014","journal-title":"J Adv Pract Oncol"},{"key":"2026052108452062000_13.9.e012747.2","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.1200\/JCO.23.01136","article-title":"Systemic therapy for melanoma: ASCO guideline update","volume":"41","author":"Seth","year":"2023","journal-title":"J Clin Oncol"},{"key":"2026052108452062000_13.9.e012747.3","unstructured":"US Food & Drug Administration (FDA) . FDA website. OPDUALAG. Available: https:\/\/www.fda.gov\/drugs\/drug-approvals-and-databases\/drug-trials-snapshot-opdualag [Accessed 22 Apr 2025]."},{"key":"2026052108452062000_13.9.e012747.4","unstructured":"European Medicines Agency (EMA) . EMA website. Opdualag. Available: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/opdualag [Accessed 22 Apr 2025]."},{"key":"2026052108452062000_13.9.e012747.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109970"},{"key":"2026052108452062000_13.9.e012747.6","doi-asserted-by":"crossref","first-page":"9502","DOI":"10.1200\/JCO.2023.41.16_suppl.9502","article-title":"Nivolumab (NIVO) plus relatlimab (RELA) vs NIVO in previously untreated metastatic or unresectable melanoma: 2-year results from RELATIVITY-047","volume":"41","author":"Tawbi","year":"2023","journal-title":"J Clin Oncol"},{"key":"2026052108452062000_13.9.e012747.7","doi-asserted-by":"crossref","first-page":"S723","DOI":"10.1016\/j.annonc.2024.08.1160","article-title":"1092P Nivolumab plus relatlimab vs nivolumab in previously untreated metastatic or unresectable melanoma: 3-year subgroup analyses from RELATIVITY-047","volume":"35","author":"Schadendorf","year":"2024","journal-title":"Ann Oncol"},{"key":"2026052108452062000_13.9.e012747.8","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1200\/JCO.24.01124","article-title":"Three-year overall survival with nivolumab plus relatlimab in advanced melanoma from RELATIVITY-047","volume":"43","author":"Tawbi","year":"2025","journal-title":"J Clin Oncol"},{"key":"2026052108452062000_13.9.e012747.9","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1200\/JCO.19.00345","article-title":"Treatment-free survival: a novel outcome measure of the effects of immune checkpoint inhibition\u2014a pooled analysis of patients with advanced melanoma","volume":"37","author":"Regan","year":"2019","journal-title":"J Clin Oncol"},{"key":"2026052108452062000_13.9.e012747.10","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003743","article-title":"Treatment-free survival over extended follow-up of patients with advanced melanoma treated with immune checkpoint inhibitors in CheckMate 067","volume":"9","author":"Regan","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2026052108452062000_13.9.e012747.11","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1200\/JCO.1989.7.1.36","article-title":"Costs and benefits of adjuvant therapy in breast cancer: a quality-adjusted survival analysis","volume":"7","author":"Goldhirsch","year":"1989","journal-title":"J Clin Oncol"},{"key":"2026052108452062000_13.9.e012747.12","doi-asserted-by":"publisher","DOI":"10.1016\/0305-7372(93)90060-5"},{"key":"2026052108452062000_13.9.e012747.13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/CMR.0000000000000793","article-title":"Sensitivity of treatment-free survival to subgroup analyses in patients with advanced melanoma treated with immune checkpoint inhibitors","volume":"32","author":"Mantia","year":"2022","journal-title":"Melanoma Res"},{"key":"2026052108452062000_13.9.e012747.14","unstructured":"Regan MM , Palaia J , Salvatore A , et al . Treatment-free survival with nivolumab + relatlimab or nivolumab in RELATIVITY-047 trial for advanced melanoma. Presented at the Society for Melanoma Research (SMR) International Congress. November 6\u20139; Philadelphia, PA, USA, 2023"},{"key":"2026052108452062000_13.9.e012747.15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709684"},{"key":"2026052108452062000_13.9.e012747.16","doi-asserted-by":"crossref","first-page":"3926","DOI":"10.1200\/JCO.24.01125","article-title":"First-line nivolumab plus relatlimab versus nivolumab plus ipilimumab in advanced melanoma: an indirect treatment comparison using RELATIVITY-047 and CheckMate 067 trial data","volume":"42","author":"Long","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026052108452062000_13.9.e012747.17","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy075"},{"key":"2026052108452062000_13.9.e012747.18","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1200\/JCO.2017.76.0983","article-title":"Patients with advanced melanoma who discontinued treatment with nivolumab and ipilimumab as a result of adverse events lived significantly longer than patients who continued treatment","volume":"36","author":"Horiguchi","year":"2018","journal-title":"J Clin Oncol"},{"key":"2026052108452062000_13.9.e012747.19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/pst.1835","article-title":"Some statistical considerations in the clinical development of cancer immunotherapies","volume":"17","author":"Huang","year":"2018","journal-title":"Pharm Stat"},{"key":"2026052108452062000_13.9.e012747.20","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-010928","article-title":"Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols","volume":"13","author":"Cottrell","year":"2025","journal-title":"J Immunother Cancer"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-012747","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:45:33Z","timestamp":1779378333000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-012747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":20,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,12]]},"published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1136\/jitc-2025-012747"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-012747","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]}}}