Intradermal priming to intravesical Bacillus Calmette-Guérin in non-muscle invasive bladder cancer: A translational research and phase I clinical trial

Objective To determine the safety and the role of modulating cytokines and proteases in the immune response to intravesical Bacillus Calmette-Guérin (BCG) when primed with systemic intradermal BCG. Methods Phase 1 and mechanistic longitudinal, prospective, single-blind randomized study (NCT04806178). Twenty-one non-muscle invasive urothelial bladder cancer patients undergoing intravesical adjuvant BCG after transurethral resection of bladder tumor (TURBT) in a teaching hospital between September 2021 and April 2023 were randomized to 0.1 mL of intradermal BCG vaccine or placebo (0.9% saline) administered 15 days before the start of intravesical BCG therapy. Blood samples were evaluated mechanistically regarding eight cytokines serum levels interferon-induced transmembrane protein 3 Gene (IFITM3), Interleukin 1 beta (IL1-BETA), interleukin-2 receptor alpha chain (IL2 RA), Interleukin 6 (IL 6), Interleukin 10 (IL 10), Tumor necrosis factor alpha (TNF-α), Interferon-β, AXL, and one protease CASPASE 8. Results After 1 exclusion, twenty patients were randomized to intradermal BCG (n = 11) and intradermal placebo (n = 9). There was no difference in adverse effects emerging from the intravesical Onco-BCG therapy, and no difference in the expression of the cytokines and proteases analyzed between control and intervention, and over time. Conclusions Intradermal BCG administration before intravesical application was safe, with no increase in adverse effects. It also does not seem to change the analyzed targets during the intravesical induction-phase BCG. Other immune targets should be explored in the future. The Brazilian tuberculosis-endemic status, where BCG vaccination is mandatory, might have affected the results.