MP70-20 B CELL CONCENTRATION IN HIGH RISK PROSTATE CANCER SPECIMENS AFTER NEOADJUVANT RITUXIMAB

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2018MP70-20 B CELL CONCENTRATION IN HIGH RISK PROSTATE CANCER SPECIMENS AFTER NEOADJUVANT RITUXIMAB Stephen Ryan, Christina Jamieson, Ahmed Shabaik, Emily Pittman, Jing Zhang, Michelle Muldong, Shabnam Shalapour, Michael Karin, Karen Messer, Stephen Howell, and Christopher Kane Stephen RyanStephen Ryan More articles by this author , Christina JamiesonChristina Jamieson More articles by this author , Ahmed ShabaikAhmed Shabaik More articles by this author , Emily PittmanEmily Pittman More articles by this author , Jing ZhangJing Zhang More articles by this author , Michelle MuldongMichelle Muldong More articles by this author , Shabnam ShalapourShabnam Shalapour More articles by this author , Michael KarinMichael Karin More articles by this author , Karen MesserKaren Messer More articles by this author , Stephen HowellStephen Howell More articles by this author , and Christopher KaneChristopher Kane More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2264AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A novel, immunosuppressive B cell subpopulation that accelerated the emergence of castrate resistant prostate cancer (PCa) was uncovered in mouse models and PCa. Murine models have demonstrated delays in PCa regrowth after ablation of B lymphocytes with rituximab. Our objective was to determine whether neoadjuvant treatment of high risk PCa patients could reduce B cell infiltration. We report B cell density in tumor and adjacent tissue for 8 patients with high risk PCa who received neoadjuvant rituximab when compared to 11 historical controls. METHODS An open label, non-randomized, single arm clinical trial for high risk PCa prior to prostatectomy (″PROTUX″ NCT01804712). Inclusion criteria were nomogram 5-year disease free prediction < 60% or Gleason sum 8, ECOG of 0-1. Subjects were candidates for prostatectomy with curative intent. Exclusion criteria were any prior treatment for PCa, metastatic disease, history of hepatitis B or C, HIV, tuberculosis, or chronic infections. Enrolled men received one cycle of rituximab (375 mg/m2 IV once weekly for 28 days), followed in 2 weeks by prostatectomy. Controls were selected from a pathologic biobank with similar patient characteristics and stained concurrently for CD20. Tumor regions were marked by a blinded pathologist and a computer algorithm quantified the immunofluorescence in tumor and adjacent tissue regions. First, mean B-cell fluorescence within the tumor was compared against historical controls. Then mean within patient difference (fluorescence tumor - fluorescence adjacent tissue) was compared against controls, both utilizing unequal variances t test. RESULTS Treated and control groups were similar in age, BMI, mean PSA at diagnosis. The treatment group experienced 10 adverse events with 4 likely related to treatment (≤ grade2), with 1 serious adverse event being a pulmonary embolism, deemed unrelated to treatment. Mean CD20 fluorescence intensity in the tumor region of the untreated and treated groups was 0.044 (95% CI 0.028 - 0.062) and 0.027 (95% CI 0.021 - 0.033) p=0.02, respectively. Mean within patient difference of CD20 fluorescence was 0.009 (95% CI -0.004 - 0.023) and -0.005 (95% CI -0.028 - 0.017) (p=0.11) in the untreated and treated groups, respectively. CONCLUSIONS Rituximab significantly decreased B cell concentration within tumors compared to historical controls and appeared to reduce the concentration of tumor resident B cells to levels comparable to adjacent normal tissue, (p=0.11 relative to controls). These results provide evidence that rituximab can modify the immune environment of the tumor. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e942 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Stephen Ryan More articles by this author Christina Jamieson More articles by this author Ahmed Shabaik More articles by this author Emily Pittman More articles by this author Jing Zhang More articles by this author Michelle Muldong More articles by this author Shabnam Shalapour More articles by this author Michael Karin More articles by this author Karen Messer More articles by this author Stephen Howell More articles by this author Christopher Kane More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...