Clinical and immunogenomic outcomes of consolidative cytoreductive nephrectomy in metastatic renal cell carcinoma patients treated with immune checkpoint blockade

You have accessJournal of UrologyCME1 Apr 2023MP28-04 CLINICAL AND IMMUNOGENOMIC OUTCOMES OF CONSOLIDATIVE CYTOREDUCTIVE NEPHRECTOMY IN METASTATIC RENAL CELL CARCINOMA PATIENTS TREATED WITH IMMUNE CHECKPOINT BLOCKADE Stephen W. Reese, Hui Jiang, Fengshen Kuo, Chih-Ying Wu, Linda H. Vuong, Eduardo A. Mascareno, Robert Motzer, Chung-Han Lee, Martin H. Voss, Ed Reznik, Victor Reuter, Johnathan Coleman, Paul Russo, Maria Carlo, Ying-Bei Chen, Ritesh R. Kotecha, and Ari Hakimi Stephen W. ReeseStephen W. Reese More articles by this author , Hui JiangHui Jiang More articles by this author , Fengshen KuoFengshen Kuo More articles by this author , Chih-Ying WuChih-Ying Wu More articles by this author , Linda H. VuongLinda H. Vuong More articles by this author , Eduardo A. MascarenoEduardo A. Mascareno More articles by this author , Robert MotzerRobert Motzer More articles by this author , Chung-Han LeeChung-Han Lee More articles by this author , Martin H. VossMartin H. Voss More articles by this author , Ed ReznikEd Reznik More articles by this author , Victor ReuterVictor Reuter More articles by this author , Johnathan ColemanJohnathan Coleman More articles by this author , Paul RussoPaul Russo More articles by this author , Maria CarloMaria Carlo More articles by this author , Ying-Bei ChenYing-Bei Chen More articles by this author , Ritesh R. KotechaRitesh R. Kotecha More articles by this author , and Ari HakimiAri Hakimi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003256.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immune checkpoint blockade (ICB) alone and in combination has improved outcomes in metastatic renal cell carcinoma (RCC). We performed in-depth clinical, histopathologic and immunogenomic analysis of a cohort of patients who were treated with upfront ICB followed by consolidative nephrectomy. This highly selected cohort included extreme responders defined by complete pathologic response and no evidence of disease at more than 25 months of follow-up. METHODS: Clinicopathologic data was collected from 32 patients who received ICB (alone or combined with anti-VEGF therapy) and then underwent resection of primary tumor. Immunogenomic analysis was performed on select pre-treatment and nephrectomy tissue using targeted next-generation sequencing (MSK-IMPACT) and immunohistochemical (IHC) staining analyses. We further performed single-cell (sc) RNA sequencing of both peripheral blood and residual tumor tissue (where available), including 4 patients who demonstrated complete pathologic response. The Kaplan-Meier method was used to calculate survival outcomes. RESULTS: All 32 patients underwent successful consolidative surgery and were further stratified based on evidence of radiographic progression, with 13 patients (40.6%) demonstrating no evidence of disease after surgery. The most common histopathology was clear cell RCC (n=29, 90.6%). Median follow-up for the cohort was 33.1 months and median OS was 45.2 months. Median OS for those who had disease progression after CN was 25.5 months and 24-month survival rate was 100% for those without progression. On pathologic evaluation, those without evidence of disease had a median of 8% (IQR: 0-35%) residual viable tumor. Mutational analysis revealed enrichment for BAP1 (n=3, 20.0% vs. n=0, 0%) and SETD2 (n=7, 46.7% vs. n=0, 0%) in patients with disease progression. scRNAseq and scTCRseq analysis of peripheral blood revealed distinct expansion of Natural Killer (NK), CD4 subsets, and unique T cell clonal expansions amongst long-term responders. Additionally, we identified an inverse relationship between NK cell populations and B cell infiltration in long-term responders. CONCLUSIONS: Delayed cytoreductive nephrectomy in select patients is associated with favorable outcomes, especially in those who demonstrate complete response after surgery. Examination of this population offers opportunities for the identification of unique tissue and peripheral-based biomarkers for long-term clinical responses in metastatic RCC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e370 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stephen W. Reese More articles by this author Hui Jiang More articles by this author Fengshen Kuo More articles by this author Chih-Ying Wu More articles by this author Linda H. Vuong More articles by this author Eduardo A. Mascareno More articles by this author Robert Motzer More articles by this author Chung-Han Lee More articles by this author Martin H. Voss More articles by this author Ed Reznik More articles by this author Victor Reuter More articles by this author Johnathan Coleman More articles by this author Paul Russo More articles by this author Maria Carlo More articles by this author Ying-Bei Chen More articles by this author Ritesh R. Kotecha More articles by this author Ari Hakimi More articles by this author Expand All Advertisement PDF downloadLoading ...