Dr Cortese on Potential Mechanisms for Improving CLL Outcomes With Venetoclax

“I wanted to…look at patients…with CLL who receive venetoclax in a standard-of-care setting to see if we could tease apart…the beneficial immunologic effects of that treatment.”

Matthew Cortese, MD, MPH, an assistant professor of oncology in the Department of Medicine – Lymphoma and the Department of Cancer Genetics and Genomics at Roswell Park Comprehensive Cancer Center, discussed the ways that his research goals informed the rationale for conducting a multiomic analysis investigating the immunologic activity of venetoclax (Venclexta) in patients with chronic lymphocytic leukemia (CLL).

Cortese works in the lab of Francisco Hernandez -Ilizaliturri, MD, at Roswell Park Comprehensive Cancer Center, where Cortese’s goal is to investigate ways to improve treatments for patients with this disease. Hernandez-Ilizaliturri’s lab focuses on studying venetoclax in cell lines.

Cortese and other CLL experts presented findings from their research at the 2024 ASH Annual Meeting. One abstract presented at the conference showed preliminary evidence that venetoclax treatment improves T-cell function, a finding that may influence future clinical trials and translational research, Cortese explained. Cortese’s own presentation at the meeting focused on outcomes of patients with CLL who received venetoclax in the standard-of-care setting. Cortese and colleagues aimed to identify potential immunologic effects of the agent that are beneficial to patients, he said.

This study showed that venetoclax can repair immune synapses in patients with CLL using mechanisms that are more complex than simply eliminating malignant CLL cells. Additionally, venetoclax repairs several immune compartments—including T cells, natural killer cells. Furthermore, venetoclax treatment induced T-cell repair mechanisms, such as shifting T cells from terminally differentiated or exhausted states toward “stem-like” states. These changes may explain why CAR T-cell toxicities were enhanced in ex vivo/in vitro killing assays that the investigators performed on cell lines. Investigators plan to validate these findings in future research that is ongoing or in development stages.