Abstract: PD48-06
Sources of Funding: 1. Max and Minnie Tomerlin Voelcker Fund_x000D_ 2. NIH 5K23CA178204-03_x000D_ 3. The Roger L. and Laura D. Zeller Charitable Foundation Chair in Urologic Cancer_x000D_

Introduction

Intravesical induction immunotherapy with Bacille Calmette-Guerin (BCG) is the standard of care treatment for high risk non-muscle invasive bladder cancer (NMIBC). Despite this, rates of recurrence and progression to muscle-invasion remain unacceptably high. We sought to optimize immunologic response to intravesical induction immunotherapy with standardized BCG intradermal vaccination prior to induction, and herein report our two year outcomes._x000D_

Methods

BCG-naive patients with high-risk NMIBC who were candidates for BCG therapy were prospectively enrolled from 2014-2015. Patients who were PPD-negative were subsequently vaccinated with BCG in standard intradermal fashion, and 3 weeks later, standard induction immunotherapy with Tice BCG was performed. Urinary cytokines, BCG-specific T and mononuclear cells, and clinical outcomes were analyzed.

Results

15 patients were enrolled and 13 completed the study; 5 controls were also enrolled. The median follow-up was 20.4 months (range: 28.1 to 14.8m). No patient experienced dose-limiting toxicity or a Grade 3+ adverse event. No patients progressed to muscle-invasive disease. 9 patients successfully converted PPD. 9 of 13 patients recurred in the lower tract (69.2%) and all were successfully salvaged. Immunologically, BCG-specific T cell lymphoproliferation was increased, as was IFN-γ secretion, IFN-γ ELISPOT response, and direct ex vivo IFN-γ response.  Flow cytometry demonstrated that BCG significantly enhanced CD4+ and CD8+ T cells in most patients.  Compared to controls, primed patients exhibited an increase in IFN-γ release in response to BCG ex vivo at both 3 months and 6 months after therapy.  Priming resulted in an earlier and more robust increase in urinary IL-2, IL-17, and IL-8 compared to control patients suggesting a potential benefit from earlier and higher activation of local immune response.

Conclusions

Vaccination with BCG prior to induction immunotherapy results in improved immunologic measurements and increased urinary cytokines associated with control of high-risk NMIBC. Priming may represent a method to increase the efficacy of BCG immunotherapy for high-risk NMIBC. Further study with dedicated multi-center clinical trials and long term follow-up is warranted._x000D_

Funding

1. Max and Minnie Tomerlin Voelcker Fund_x000D_ 2. NIH 5K23CA178204-03_x000D_ 3. The Roger L. and Laura D. Zeller Charitable Foundation Chair in Urologic Cancer_x000D_