{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:40:33Z","timestamp":1792798833659,"version":"4.5.0"},"reference-count":28,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["annalsofoncology.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Annals of Oncology"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.annonc.2026.10.103","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:08:58Z","timestamp":1792739338000},"update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nivolumab plus relatlimab with platinum-doublet chemotherapy versus nivolumab with platinum-doublet chemotherapy in stage IV or recurrent non-small cell lung cancer: clinical, translational, and patient-reported outcomes results from the phase II RELATIVITY-104 study"],"prefix":"10.1016","author":[{"given":"N.","family":"Girard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Burotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.G.","family":"Paz-Ares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Schenker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lingua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Orlandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Naidoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.K.","family":"Beardsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Velcheti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.L.","family":"Martinengo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Felip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5348-4462","authenticated-orcid":false,"given":"M.","family":"Reck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Qureshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Kasbekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Samanta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7137-3953","authenticated-orcid":false,"given":"J.","family":"Neely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Garnett-Benson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.X.","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3402-1144","authenticated-orcid":false,"given":"M.","family":"Cobo-Dols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.annonc.2026.10.103_bib1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3389\/fimmu.2019.00453","article-title":"Combining immune checkpoint inhibitors: established and emerging targets and strategies to improve outcomes in melanoma","volume":"10","author":"Khair","year":"2019","journal-title":"Front Immunol"},{"issue":"19","key":"10.1016\/j.annonc.2026.10.103_bib2","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1\u2013positive non\u2013small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N Engl J Med"},{"issue":"21","key":"10.1016\/j.annonc.2026.10.103_bib3","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1056\/NEJMoa1810865","article-title":"Pembrolizumab plus chemotherapy for squamous non\u2013small-cell lung cancer","volume":"379","author":"Paz-Ares","year":"2018","journal-title":"N Engl J Med"},{"issue":"14","key":"10.1016\/j.annonc.2026.10.103_bib4","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1200\/JCO.19.03136","article-title":"Updated analysis from KEYNOTE-189: pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non-small-cell lung cancer","volume":"38","author":"Gadgeel","year":"2020","journal-title":"J Clin Oncol"},{"issue":"10183","key":"10.1016\/j.annonc.2026.10.103_bib5","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/S0140-6736(18)32409-7","article-title":"Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial","volume":"393","author":"Mok","year":"2019","journal-title":"Lancet"},{"issue":"24","key":"10.1016\/j.annonc.2026.10.103_bib6","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1056\/NEJMoa1716948","article-title":"Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC","volume":"378","author":"Socinski","year":"2018","journal-title":"N Engl J Med"},{"issue":"21","key":"10.1016\/j.annonc.2026.10.103_bib7","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1056\/NEJMoa1910231","article-title":"Nivolumab plus ipilimumab in advanced non\u2013small-cell lung cancer","volume":"381","author":"Hellmann","year":"2019","journal-title":"N Engl J Med"},{"issue":"2","key":"10.1016\/j.annonc.2026.10.103_bib8","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S1470-2045(20)30641-0","article-title":"First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial","volume":"22","author":"Paz-Ares","year":"2021","journal-title":"Lancet Oncol"},{"issue":"5-6","key":"10.1016\/j.annonc.2026.10.103_bib9","doi-asserted-by":"crossref","first-page":"176","DOI":"10.18632\/genesandcancer.180","article-title":"The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy","volume":"9","author":"Long","year":"2018","journal-title":"Genes Cancer"},{"key":"10.1016\/j.annonc.2026.10.103_bib10","doi-asserted-by":"crossref","unstructured":"Feng J, Yang H, Zhang Y et al. Tumor cell-derived lactate induces TAZ-dependent upregulation of PD-L1 through GPR81 in human lung cancer cells Oncogene 2017; 36(42): 5829-5839.","DOI":"10.1038\/onc.2017.188"},{"issue":"10","key":"10.1016\/j.annonc.2026.10.103_bib11","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1158\/2326-6066.CIR-22-0057","article-title":"Preclinical characterization of relatlimab, a human LAG-3-blocking antibody, alone or in combination with nivolumab","volume":"10","author":"Thudium","year":"2022","journal-title":"Cancer Immunol Res"},{"issue":"4","key":"10.1016\/j.annonc.2026.10.103_bib12","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1158\/0008-5472.CAN-11-1620","article-title":"Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape","volume":"72","author":"Woo","year":"2012","journal-title":"Cancer Res"},{"issue":"1","key":"10.1016\/j.annonc.2026.10.103_bib13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nri3790","article-title":"Clinical blockade of PD1 and LAG3--potential mechanisms of action","volume":"15","author":"Nguyen","year":"2015","journal-title":"Nat Rev Immunol"},{"issue":"5","key":"10.1016\/j.annonc.2026.10.103_bib14","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"issue":"1","key":"10.1016\/j.annonc.2026.10.103_bib15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"New Engl J Med"},{"key":"10.1016\/j.annonc.2026.10.103_bib16","unstructured":"European Medicines Agency. Opdulag. Available at https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/opdualag. 2022. Accessed January 8, 2026."},{"key":"10.1016\/j.annonc.2026.10.103_bib17","unstructured":"Food and Drug Administration. FDA approves opdualag for unresectable or metastatic melanoma. Available at https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-opdualag-unresectable-or-metastatic-melanoma. 2022. Accessed January 8, 2026."},{"issue":"suppl 2","key":"10.1016\/j.annonc.2026.10.103_bib18","article-title":"Nivolumab (NIVO) plus relatlimab with platinum-doublet chemotherapy (PDCT) vs NIVO + PDCT as first-line (1L) treatment (tx) for stage IV or recurrent NSCLC: results from the randomized phase II RELATIVITY-104 study","volume":"35","author":"Girard","year":"2024","journal-title":"Ann Oncol"},{"issue":"28","key":"10.1016\/j.annonc.2026.10.103_bib19","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1200\/JCO.2015.62.3488","article-title":"Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline update","volume":"33","author":"Smith","year":"2015","journal-title":"J Clin Oncol"},{"issue":"suppl 5","key":"10.1016\/j.annonc.2026.10.103_bib20","doi-asserted-by":"crossref","first-page":"v111","DOI":"10.1093\/annonc\/mdw325","article-title":"Management of febrile neutropaenia: ESMO Clinical Practice Guidelines","volume":"27","author":"Klastersky","year":"2016","journal-title":"Ann Oncol"},{"issue":"17","key":"10.1016\/j.annonc.2026.10.103_bib21","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1158\/1078-0432.CCR-24-2499","article-title":"Unraveling relatlimab-specific biology using biomarker analyses in patients with advanced melanoma in RELATIVITY-047","volume":"31","author":"Lipson","year":"2025","journal-title":"Clin Cancer Res"},{"issue":"suppl","key":"10.1016\/j.annonc.2026.10.103_bib22","doi-asserted-by":"crossref","first-page":"8526","DOI":"10.1200\/JCO.2025.43.16_suppl.8526","article-title":"Characterization of histology-dependent immunobiological differences in metastatic NSCLC: implications for treatment with PD-1 and LAG-3 inhibitors","volume":"43","author":"Borghaei","year":"2025","journal-title":"J Clin Oncol"},{"issue":"24","key":"10.1016\/j.annonc.2026.10.103_bib23","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.120360","article-title":"Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3\/FCRL6 engagement","volume":"3","author":"Johnson","year":"2018","journal-title":"JCI Insight"},{"issue":"127","key":"10.1016\/j.annonc.2026.10.103_bib24","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3003689","article-title":"Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape","volume":"4","author":"Taube","year":"2012","journal-title":"Sci Transl Med"},{"issue":"16","key":"10.1016\/j.annonc.2026.10.103_bib25","doi-asserted-by":"crossref","first-page":"4336","DOI":"10.1016\/j.cell.2024.07.018","article-title":"LAG-3 sustains TOX expression and regulates the CD94\/NKG2-Qa-1b axis to govern exhausted CD8 T cell NK receptor expression and cytotoxicity","volume":"187","author":"Ngiow","year":"2024","journal-title":"Cell"},{"issue":"16","key":"10.1016\/j.annonc.2026.10.103_bib26","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.1016\/j.cell.2024.07.016","article-title":"LAG-3 and PD-1 synergize on CD8+ T cells to drive T cell exhaustion and hinder autocrine IFN-\u03b3-dependent anti-tumor immunity","volume":"187","author":"Andrews","year":"2024","journal-title":"Cell"},{"issue":"1","key":"10.1016\/j.annonc.2026.10.103_bib27","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1186\/s12885-021-08323-4","article-title":"Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of 6 randomized trials","volume":"21","author":"Gargiulo","year":"2021","journal-title":"BMC Cancer"},{"key":"10.1016\/j.annonc.2026.10.103_bib28","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.866561","article-title":"High levels of circulating monocytic myeloid-derived suppressive-like cells are associated with the primary resistance to immune checkpoint inhibitors in advanced non-small cell lung cancer: an exploratory analysis","volume":"13","author":"Bronte","year":"2022","journal-title":"Front Immunol"}],"container-title":["Annals of Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0923753426068857?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0923753426068857?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:09:47Z","timestamp":1792796987000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0923753426068857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":28,"alternative-id":["S0923753426068857"],"URL":"https:\/\/doi.org\/10.1016\/j.annonc.2026.10.103","relation":{},"ISSN":["0923-7534"],"issn-type":[{"value":"0923-7534","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nivolumab plus relatlimab with platinum-doublet chemotherapy versus nivolumab with platinum-doublet chemotherapy in stage IV or recurrent non-small cell lung cancer: clinical, translational, and patient-reported outcomes results from the phase II RELATIVITY-104 study","name":"articletitle","label":"Article Title"},{"value":"Annals of Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.annonc.2026.10.103","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology.","name":"copyright","label":"Copyright"}]}}