Suzanne Merrill, MD, on the rationale for BCG plus PD-1/PD-L1 inhibitors in high-risk NMIBC

With BCG is still the standard-of-care treatment option for patients with high-risk non–muscle invasive bladder cancer (NMIBC), high recurrence rates present the need for novel therapies for this patient population, according to Suzanne B. Merrill, MD, FACS.

In a recent interview with Urology Times®, Merrill touched on the historical landscape of BCG monotherapy, as well as the emergence of novel regimens combining BCG with immune checkpoint inhibitors (ICIs) in the BCG-naïve setting.

She noted, “Even though BCG has a really high initial complete response, so we see patients do well initially, the unfortunateness is the durability, and that goes back at those how we get those high recurrence rates.”

Merrill is a urologic oncologist at Colorado Urology, an affiliate of United Urology Group.

According to Merrill, the rationale for combining BCG with ICIs in this setting is because of the apparent synergy between the 2 therapies. She explained that BCG innates a strong inflammatory response, “almost priming the tumor microenvironment and ultimately making it more responsive to immune checkpoint inhibition.”

She also added that BCG can upregulate PD-L1 expression on tumor cells. This is important, since ICIs act by blocking PD-L1 receptors, “therefore enhancing the anti-tumor effect that they can enact,” she said.Lastly, she explained that BCG may also help upregulate the production of pro-inflammatory cytokines, which can further enhance the effectiveness of ICIs.

Overall, she concluded, “BCG [may be] enacting this strong inflammatory response [and] upregulating cytotoxic T cells, but if the tumor outsmarts that, that's when we need something else there to help create that anti-tumor effect. We're learning that use of ICIs, immune checkpoint inhibitors, could be one solution to that.”