559 Clustering by metastatic sites predicts overall survival and describes patterns of progression for patients with metastatic melanoma after immunotherapy

• DOI: 10.1136/jitc-2024-sitc2024.0559
• Publication Date: 2024-11-05T14:58:58Z
• Authors: Daniel Y Lee; Alexander Pan; Tyler Aprati; Mario Sznol; David Liu; Jeffrey Ishizuka

<h3>Background</h3> While certain sites of metastatic melanoma are associated with worse outcomes after immunotherapy, such as brain and liver, parsimonious models to risk stratify disease describe patterns progression notwell established.^{1 2} Risk stratification patients advanced remains paramount weigh the benefits ipilimumab+nivolumab (ipi/nivo) its increased toxicity compared anti-PD1 monotherapy.³ In this study, we aim identify different phenotypes melanoma. <h3>Methods</h3> This retrospective study utilized US-based Flatiron Health electronic health record-derived de- identified databaseincluding treated first-line immunotherapy (ipi/nivo, monotherapy, or nivo+relatlimab). Demographics, variables, andclinical were summarized chi-squared t-test. Overall survival (OS) was estimated via Kaplan Meier method log- rank test; hazard ratios computed Cox regression. Unbiased Bernoulli mixture (BMM) cluster by using Rpackage 'flexmix'. Cluster number optimized Bayesian information criterion. <h3>Results</h3> Of 4,521 patients, at diagnosis evaluated (table 1, figure 1A-B). Pleural, spleen, brain, bone metastases particularly OS (figure 1C). We a BMM 11 most frequent lifetime form 5 clusters: high burden (HMB,n=748), avid (BA, n=838), liver (LivA, n=866), lymph node (LNA, n=969), lung (LunA,n=830, 2A). LunA (median 59.8 months) LNA 62.0 greater than for HMB 16.3 months), BA 20.1 LivA 17.8 months,p&lt;0.001 all comparisons, 2B). Patients in younger those LivA, LNA, clusters (p&lt;0.001 all, table 2). HMB, BA, received ipi/nivo more andLunA BRAF NRAS mutations both), no driver mutation Clustering yielded similar clusters, 38.7% transitioning from last follow up 3). <h3>Conclusions</h3> had disease. These may represent novel schema stratifying <h3>References</h3> Yu J, Green MD, Li S, Sun Y, Journey SN, Choi JE, Rizvi SM, Qin A, Waninger JJ, Lang X, Chopra Z, El Naqa I, Zhou Bian Jiang L, Tezel Skvarce Achar RK, Sitto M, Rosen BS, Su F, Narayanan SP, Cao Wei Szeliga W, Vatan Mayo C, Morgan MA, Schonewolf CA, Cuneo K, Kryczek Ma VT, Lao CD, Lawrence TS, Ramnath N, Wen Chinnaiyan AM, Cieslik Alva Zou W. Liver metastasis restrains efficacy macrophage-mediated T cell elimination. <i>Nat Med</i> 2021 Jan;<b>27</b>(1):152–164. doi: 10.1038/s41591-020-1131-x. Epub Jan 4. PMID: 33398162; PMCID: PMC8095049. Pires da Silva Lo Quek Gonzalez Carlino MS, Long GV, Menzies AM. Site-specific response patterns, pseudoprogression, acquired resistance ipilimumab combined anti-PD-1 therapy. <i>Cancer</i> 2020 1;<b>126</b>(1):86–97. 10.1002/cncr.32522. 2019 Oct 31584722. Wolchok JD, Chiarion-Sileni V, R, Rutkowski P, Grob Cowey CL, Wagstaff Schadendorf D, Ferrucci PF, Smylie Dummer Hill Hogg Haanen Bechter O, Maio Marquez-Rodas Guidoboni McArthur G, Lebbé Ascierto PA, Cebon Sosman Postow Callahan MK, Walker Rollin Bhore Hodi FS, Larkin J. nivolumab melanoma.<i> N Engl J 2017 5;<b>377</b>(14):1345–1356. 10.1056/NEJMoa1709684. <i>Epub</i> Sep 11. Erratum in: <i>N 2018 Nov 29;<b>379</b>(22):2185. 10.1056/NEJMx180040. 28889792; PMC5706778. <h3>Ethics Approval</h3> approved Yale University Institutional Review Board, IRB ID 2000036075.