Mp16-07 Urinary Minimal Residual Disease Detection Predicts Recurrence in BCG-Unresponsive Nimbc and Quantifies Molecular Response to Nadofaragene Firadenovec

You have accessJournal of UrologyBladder Cancer: Non-invasive I (MP16)1 May 2024MP16-07 URINARY MINIMAL RESIDUAL DISEASE DETECTION PREDICTS RECURRENCE IN BCG-UNRESPONSIVE NIMBC AND QUANTIFIES MOLECULAR RESPONSE TO NADOFARAGENE FIRADENOVEC Vikram M. Narayan, Come Tholomier, Sharada Mokkapati, Alberto Martini, Vincent M. Caruso, Brian C. Mazzarella, Kevin G. Phillips, Vincent T. Bicocca, Trevor G. Levin, David Sawutz, Seppo Yla-Herttuala, Nigel Parker, David J. McConkey, and Colin P. N. Dinney Vikram M. NarayanVikram M. Narayan , Come TholomierCome Tholomier , Sharada MokkapatiSharada Mokkapati , Alberto MartiniAlberto Martini , Vincent M. CarusoVincent M. Caruso , Brian C. MazzarellaBrian C. Mazzarella , Kevin G. PhillipsKevin G. Phillips , Vincent T. BicoccaVincent T. Bicocca , Trevor G. LevinTrevor G. Levin , David SawutzDavid Sawutz , Seppo Yla-HerttualaSeppo Yla-Herttuala , Nigel ParkerNigel Parker , David J. McConkeyDavid J. McConkey , and Colin P. N. DinneyColin P. N. Dinney View All Author Informationhttps://doi.org/10.1097/01.JU.0001008640.01272.9d.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary minimal residual disease (uMRD) profiling uses next-generation sequencing to identify mutations associated with urothelial carcinoma and can be used to predict recurrence and assess response to therapy. Nadofaragene firadenovec is a novel intravesical therapy recently approved for BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC). We evaluate the utility of uMRD to identify molecular response to Nadofaragene in patients with high-grade (HG) BCG-refractory or relapsed NMIBC. METHODS: This was an open-label, multicenter, parallel-arm, phase II study (NCT01687244) of 43 patients with BCG-unresponsive NMIBC who received intravesical nadofaragene. The primary endpoint was 12-month HG-recurrence-free survival (RFS). All patients who received at least one dose were included in the uMRD analysis. Urine samples were collected prior to induction and at 3 months. uMRD testing was done using the UroAmp MRD assay, which identifies single-nucleotide variants, copy-number variants (CNVs), insertion-deletions, copy-neutral loss of heterozygosity, microsatellite instability, and aneuploidy. RESULTS: Among evaluable patients (n=35), initial pathological stages were Ta (n=3), T1 (n=9), and Tis (n=23), with concomitant CIS in six patients. In pre-treatment urine (n=32), TP53, TERT, PIK3CA, ARID1A, PLEKHS1, ELF3, and ERBB2 were among the most prevalently mutated genes. Most CNVs occurred in SOX4 and NIT1. uMRD identified patients with high (72%) and low (28%) recurrence risk in both pre- and post-induction collections. At 12 months, post-induction RFS rate was 100% for low-risk and 38% for high-risk patients (p=0.038, log-rank test). Pre-induction RFS was 56% for low-risk and 22% for high-risk (p=0.097, log-rank test). Using matched pre- and post-induction urine (n=15), quantitative drug response was measured and patients categorized as MRD Negative (7%), MRD Complete Responder (13%), MRD Partial Responder (27%), MRD Stable (20%), or MRD Refractory (33%). Recurrence correlated broadly with response groups: MRD Negative and Complete Responder groups did not recur on study, while 7 of 12 patients in the other groups recurred. CONCLUSIONS: uMRD enables quantitative assessment of molecular response to drug treatment. uMRD-determined pre-treatment disease burden assessment can support stratification of control and intervention arms in future treatment trials. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e242 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Vikram M. Narayan More articles by this author Come Tholomier More articles by this author Sharada Mokkapati More articles by this author Alberto Martini More articles by this author Vincent M. Caruso More articles by this author Brian C. Mazzarella More articles by this author Kevin G. Phillips More articles by this author Vincent T. Bicocca More articles by this author Trevor G. Levin More articles by this author David Sawutz More articles by this author Seppo Yla-Herttuala More articles by this author Nigel Parker More articles by this author David J. McConkey More articles by this author Colin P. N. Dinney More articles by this author Expand All Advertisement PDF downloadLoading ...