PD43-05 IMMUNOMODULATORY RESPONSE TO NEOADJUVANT NIVOLUMAB IN NON-METASTATIC CLEAR CELL RENAL CELL CARCINOMA: RESULTS FROM a PHASE I TRIAL

You have accessJournal of UrologyCME1 Apr 2023PD43-05 IMMUNOMODULATORY RESPONSE TO NEOADJUVANT NIVOLUMAB IN NON-METASTATIC CLEAR CELL RENAL CELL CARCINOMA: RESULTS FROM a PHASE I TRIAL Nirmish Singla, Thomas Nirschl, Aleksandar Obradovic, Eugene Shenderov, Kara Lombardo, Xiaopu Liu, Alice Pons, Jelani Zarif, Steven Rowe, Bruce Trock, Hans Hammers, Trinity Bivalacqua, Phillip Pierorazio, Julie Deutsch, Tamara Lotan, Janis Taube, Yasser Ged, Michael Gorin, Mohamad Allaf, and Charles Drake Nirmish SinglaNirmish Singla More articles by this author , Thomas NirschlThomas Nirschl More articles by this author , Aleksandar ObradovicAleksandar Obradovic More articles by this author , Eugene ShenderovEugene Shenderov More articles by this author , Kara LombardoKara Lombardo More articles by this author , Xiaopu LiuXiaopu Liu More articles by this author , Alice PonsAlice Pons More articles by this author , Jelani ZarifJelani Zarif More articles by this author , Steven RoweSteven Rowe More articles by this author , Bruce TrockBruce Trock More articles by this author , Hans HammersHans Hammers More articles by this author , Trinity BivalacquaTrinity Bivalacqua More articles by this author , Phillip PierorazioPhillip Pierorazio More articles by this author , Julie DeutschJulie Deutsch More articles by this author , Tamara LotanTamara Lotan More articles by this author , Janis TaubeJanis Taube More articles by this author , Yasser GedYasser Ged More articles by this author , Michael GorinMichael Gorin More articles by this author , Mohamad AllafMohamad Allaf More articles by this author , and Charles DrakeCharles Drake More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003353.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We sought to (1) elucidate the effects of PD-1 inhibition on primary tumor-infiltrating and circulating immune cell populations in ccRCC and (2) correlate tumor microenvironment and circulating immune cell compositions with response to anti-PD-1 therapy. METHODS: We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from this cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response using fluorescence-activated cell sorting, bulk RNA sequencing with protein activity inference, and enzyme-linked immunosorbent assay for circulating cytokines. RESULTS: We found that nivolumab durably promotes a pro-inflammatory state within the primary tumor, as evidenced by a sustained increase in the effector T cell phenotype and decreased representation of regulatory T cell subsets. Baseline immune infiltration within the primary tumor including T effector and myeloid enrichment along with angiogenic depletion correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. CONCLUSIONS: Our findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations. Source of Funding: Bristol Myers Squibb © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1119 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nirmish Singla More articles by this author Thomas Nirschl More articles by this author Aleksandar Obradovic More articles by this author Eugene Shenderov More articles by this author Kara Lombardo More articles by this author Xiaopu Liu More articles by this author Alice Pons More articles by this author Jelani Zarif More articles by this author Steven Rowe More articles by this author Bruce Trock More articles by this author Hans Hammers More articles by this author Trinity Bivalacqua More articles by this author Phillip Pierorazio More articles by this author Julie Deutsch More articles by this author Tamara Lotan More articles by this author Janis Taube More articles by this author Yasser Ged More articles by this author Michael Gorin More articles by this author Mohamad Allaf More articles by this author Charles Drake More articles by this author Expand All Advertisement PDF downloadLoading ...