Pd51-12 Comprehensive Immunogenomic Evaluation of Patients Undergoing Consolidative Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma Patients Treated With Immune Checkpoint Blockade

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II (PD51)1 May 2024PD51-12 COMPREHENSIVE IMMUNOGENOMIC EVALUATION OF PATIENTS UNDERGOING CONSOLIDATIVE CYTOREDUCTIVE NEPHRECTOMY IN METASTATIC RENAL CELL CARCINOMA PATIENTS TREATED WITH IMMUNE CHECKPOINT BLOCKADE Stephen Reese, Vijay Yarlagadda, Chih-Ying Wu, Fengshen Kuo, Cerise Tang, Hui Jiang, Mark Dawidek, Lynda H. Vuong, Lennert Eismann, Robert Motzer, Ed Reznik, Victor S. Reuter, Johnathan S. Coleman, Paul S. Russo, Ritesh R. Kotecha, Christina S. Leslie, Yingbei Chen, and A. Ari S. Hakimi Stephen ReeseStephen Reese , Vijay YarlagaddaVijay Yarlagadda , Chih-Ying WuChih-Ying Wu , Fengshen KuoFengshen Kuo , Cerise TangCerise Tang , Hui JiangHui Jiang , Mark DawidekMark Dawidek , Lynda H. VuongLynda H. Vuong , Lennert EismannLennert Eismann , Robert MotzerRobert Motzer , Ed ReznikEd Reznik , Victor S. ReuterVictor S. Reuter , Johnathan S. ColemanJohnathan S. Coleman , Paul S. RussoPaul S. Russo , Ritesh R. KotechaRitesh R. Kotecha , Christina S. LeslieChristina S. Leslie , Yingbei ChenYingbei Chen , and A. Ari S. HakimiA. Ari S. Hakimi View All Author Informationhttps://doi.org/10.1097/01.JU.0001009360.84490.42.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immune checkpoint blockade (ICB) alone and in combination has dramatically 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 cytoreductive 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 41 patients who received ICB (alone or combined with anti-VEGF therapy) and then subsequently 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. To expand the genomic analysis, we included all patients with whom we could identify at our institution if the sequencing was performed in the treatment naïve vs. post-treatment setting (n=318). We further performed single-cell (sc)RNA sequencing of both peripheral blood and residual tumor tissue (where available), including 6 patients who demonstrated exceptional response to therapy (=<10% residual viable tumor). The Kaplan-Meier method was used to calculate survival outcomes. RESULTS: All 41 patients underwent successful consolidative surgery and were further stratified based on pathologic response at time of surgery into patients who had minimal residual disease on pathology (0-10%) vs. all others. There were (n=13) or 29.3% of cohort who were consider to have had an ER. No patients who demonstrated an exceptional response on pathology had evidence of progression or died of kidney cancer. In the non-exceptional responder group, median PFS was 10.9 mo (7.9-NR, p=0.001) and overall survival was 33.1 mo (23.9-NR, p=0.06) and those without evidence of progression had a median of 8% (IQR: 0-35%) residual viable tumor. Mutational analysis revealed enrichment in the post-treatment setting for unique gene signatures. Amongst ER patients, scRNA and TCR analysis of peripheral blood revealed distinct expansion of CD8+ cytotoxic T cells, large proportion of CD4+ naive cells with unique sub-clones and CD8+ tissue resident cells. CONCLUSIONS: Delayed cytoreductive nephrectomy in selected patients is associated with favorable outcomes and offers unique opportunities for tissue and peripheral based biomarkers for long term clinical responses in metastatic RCC. Patients who demonstrate an exceptional pathologic response may have a favorable prognosis. Source of Funding: MSKCC Institutional Grant © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1071 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Stephen Reese More articles by this author Vijay Yarlagadda More articles by this author Chih-Ying Wu More articles by this author Fengshen Kuo More articles by this author Cerise Tang More articles by this author Hui Jiang More articles by this author Mark Dawidek More articles by this author Lynda H. Vuong More articles by this author Lennert Eismann More articles by this author Robert Motzer More articles by this author Ed Reznik More articles by this author Victor S. Reuter More articles by this author Johnathan S. Coleman More articles by this author Paul S. Russo More articles by this author Ritesh R. Kotecha More articles by this author Christina S. Leslie More articles by this author Yingbei Chen More articles by this author A. Ari S. Hakimi More articles by this author Expand All Advertisement PDF downloadLoading ...