Long-term survival and biomarker analysis evaluating neoadjuvant plus adjuvant relatlimab (anti-LAG3) and nivolumab (anti-PD1) in patients with resectable melanoma Journal Article


Authors: Burton, E. M.; Milton, D. R.; Tetzlaff, M. T.; Wani, K.; Ross, M. I.; Postow, M. A.; Lazcano, R.; Glitza, I. C.; Wong, M. K.; Patel, S. P.; Diab, A.; Gershenwald, J. E.; McQuade, J. L.; Betof Warner, A.; Prieto, V. G.; Lee, J. E.; Goepfert, R. P.; Fisher, S. B.; Song, A.; Malke, J.; Simon, J. M.; Ariyan, C.; Torres-Cabala, C. A.; Davies, M. A.; Lazar, A.; Wargo, J. A.; Tawbi, H. A.; Amaria, R. N.
Article Title: Long-term survival and biomarker analysis evaluating neoadjuvant plus adjuvant relatlimab (anti-LAG3) and nivolumab (anti-PD1) in patients with resectable melanoma
Abstract: Immune checkpoint blockade (ICB) has revolutionized outcomes for patients with melanoma across multiple disease settings. In patients with advanced, unresectable disease, the ICB combination of nivolumab (anti-PD1) and relatlimab (anti-LAG-3) has demonstrated improved clinical outcomes compared with nivolumab monotherapy. There exists an unmet need to identify biomarkers that predict response to this combination regimen and rational therapeutic strategies to overcome resistance. We previously reported the initial results of a phase II clinical trial (ClinicalTrials.gov identifier: NCT02519322) of neoadjuvant systemic treatment (NST) followed by adjuvant treatment with nivolumab and relatlimab, which achieved a major pathologic response (MPR; ≤10% viable tumor) rate of 63% in patients with stage III/IV, surgically resectable melanoma. Our updated clinical follow-up (median 47 months) for these patients demonstrates that at 4 years from the start of NST, 80% of patients remain event-free, including 95% of patients who achieved a MPR. Gene expression analysis of longitudinally collected biospecimens from the trial identifies baseline upregulation of several immune modulatory pathways associated with MPR; by contrast, increased B7-H3 expression was associated with resistance. This work demonstrates the long-term benefit of neoadjuvant nivolumab and relatlimab and identifies a potentially targetable predictor of resistance to this combination therapy. © 2025 American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Publication status: Online ahead of print
Date Published: 2025-07-10
Online Publication Date: 2025-07-10
Language: English
DOI: 10.1200/jco-25-00494
PROVIDER: scopus
PMCID: PMC12252214
PUBMED: 40638872
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA0087480) acknowledged in PubMed and PDF -- Source: Scopus
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  1. Michael Andrew Postow
    367 Postow
  2. Charlotte Eielson Ariyan
    155 Ariyan