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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (28)
Elizabeth M. Burton
Denái R. Milton
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
Michael T. Tetzlaff
Khalida Wani
Merrick I. Ross
Michael A. Postow
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Rossana Lazcano
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Isabella C. Glitza
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Michael K. Wong
Sapna P. Patel
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Adi Diab
The University of Texas MD Anderson Cancer Center
Jeffrey E. Gershenwald
Jennifer L. McQuade
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Allison Betof Warner
Stanford University School of Medicine, Stanford University, Stanford, CA
Victor G. Prieto
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Jeffrey E. Lee
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Ryan P. Goepfert
Sarah B. Fisher
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Addison Song
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Jared Malke
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Julie M. Simon
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Charlotte Ariyan
Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Carlos A. Torres-Cabala
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
Michael A. Davies
Alexander Lazar
Jennifer A. Wargo
Hussein A. Tawbi
The University of Texas MD Anderson Cancer Center, Houston, TX
Rodabe N. Amaria
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX