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An independent validation cohort (n\u2009=\u200979) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR\u2009=\u20094.01, 95% CI 2.10\u20137.67, Cox <jats:italic>P<\/jats:italic>\u2009=\u20092.63e\u221205) and PFS (HR\u2009=\u20093.72, 95% CI 2.06\u20136.73, Cox <jats:italic>P<\/jats:italic>\u2009=\u20091.38e\u221205) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-\u03b3 signature expression, TMB, age, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR\u2009=\u20092.76, 95% CI 1.24\u20136.13, Cox <jats:italic>P<\/jats:italic>\u2009=\u20090.0131). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR\u2009=\u20091.98, 95% CI 1.16\u20133.38; Cox <jats:italic>P<\/jats:italic>\u2009=\u20090.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR\u2009=\u20092.12, 95% CI 1.2\u20133.72, Cox <jats:italic>P<\/jats:italic>\u2009=\u20090.00925) and PFS (LDH-adjusted HR\u2009=\u20091.91, 95% CI 1.08\u20133.38, Cox <jats:italic>P<\/jats:italic>\u2009=\u20090.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH.<\/jats:p>","DOI":"10.1038\/s41598-024-61150-y","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T17:01:57Z","timestamp":1715878917000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma"],"prefix":"10.1038","volume":"14","author":[{"given":"Lindsay V. M.","family":"Leek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C. 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J.H. has provided consultation, attended advisory boards, and\/or provided lectures for BMS, CureVac, GSK, Imcyse, Iovance Bio, Instil Bio, Immunocore, Ipsen, Merck Serono, MSD, Molecular Partners, Novartis, Pfizer, Roche\/Genentech, Sanofi, Scenic, Third Rock Ventures, has participated in the SAB of Achilles Tx, BioNTech US, Instil Bio, PokeAcell, T-Knife, Scenic and Neogene Therapeutics. Through this, the NKI has received grant support from Amgen, Asher Bio, BioNTech, BMS, MSD, Novartis, and Sastra Cell Therapy. MA has advisory board\/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, and Bayer. J.H has received research grants from Merck-Pfizer that were paid to the institute and not related to current work.\u00a0M.A. has advisory board\/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, and Bayer. Research grants Merck-Pfizer. Not related to current work and paid to the institute. F.v.d.B receives a speaker fee for Merck. Not related to current work and paid to the institute. The other authors reported no disclosures.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11244"}}