Dr Hernandez-Ilizaliturri on the Design of an Observational Study of Immunologic Changes With Venetoclax in CLL

"We wanted to demonstrate that venetoclax—through [a potential improvement] in the T-cell fitness [in] patients with CLL—could enhance the capacity to generate better CAR T cells in those patients, which may enable them to kill lymphoma [cells] more efficiently than patients with CLL who have not received this kind of treatment."

Francisco J. Hernandez-Ilizaliturri, MD, a professor of oncology in the Department of Medicine – Lymphoma, the director of Lymphoma Research, the head of the Lymphoma Translational Research Lab, and an associate professor in the Department of Immunology at Roswell Park Comprehensive Cancer Center, as well as a clinical professor in the Department of Medicine at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, outlined the design and objectives of an observational study investigating immunologic changes associated with venetoclax (Venclexta) in patients with chronic lymphocytic leukemia (CLL).

Given the profound immune dysregulation observed in CLL—including T-cell exhaustion and impaired immune surveillance—there is increasing interest in identifying therapeutic approaches that could restore immune competence, Hernandez-Ilizaliturri explained. Venetoclax, a selective BCL-2 inhibitor approved for use in CLL, may offer cytoreductive benefit and the potential to modulate the immune microenvironment, he noted.

The observational study was designed to evaluate the effects of venetoclax on peripheral immune cell dynamics over time. Patients with CLL receiving standard-of-care venetoclax were enrolled, and they provided serial peripheral blood samples, allowing investigators to monitor both leukemic and immune cell compartments. Hernandez-Ilizaliturri stated that the study aimed to characterize baseline immune cell fitness and to assess whether venetoclax treatment leads to improvements in T-cell functionality, particularly with respect to cytolytic potential and phenotypic markers of exhaustion.

A key translational goal of this investigation is to determine whether venetoclax-exposed T cells demonstrate improved capacity for ex vivo manipulation and expansion, such as in the context of CAR T-cell therapy. Hernandez-Ilizaliturri emphasized that patients with untreated or refractory CLL may exhibit diminished CAR T-cell manufacturing success due to intrinsic T-cell dysfunction, which this study seeks to better understand.