Dr Hernandez-Ilizaliturri on the Implications of Immunologic Changes With Venetoclax in CLL

“Clinically, we do hope that patients who have CLL…and [require] CAR T-cell therapy [could potentially receive] combined BCL-2 inhibitors with T-cell engaging therapy as a way to improve the success that we’re seeing with this particular class of agents.”

Francisco J. Hernandez-Ilizaliturri, MD, professor, oncology, Department of Medicine – Lymphoma, director, Lymphoma Research, head, Lymphoma Translational Research Lab, associate professor, Department of Immunology, Roswell Park Comprehensive Cancer Center; clinical professor, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, details the clinical implications of immunologic changes observed with venetoclax (Venclexta) treatment in patients with chronic lymphocytic leukemia (CLL).

Based on preliminary findings from an analysis presented at the 2024 ASH Annual meeting, more studies with a larger patient population need to be conducted to further identify whether venetoclax contributes to T-cell repair, Hernandez-Ilizaliturri begins. Looking forward, he notes that patients with CLL who require CAR T-cell therapy will hopefully have the potential to be treated with BCL-2 inhibitors with T-cell engaging therapy to improve the success of treatment outcomes. He emphasizes that although CAR T-cell therapy has shown great efficacy in patients with large B-cell lymphoma, the activity has not been as robust for patients with CLL. However, there is a margin to further improve this for those with CLL, he says.

Specifically, the findings from the analysis demonstrated that multiple immune compartments, such as T cells, natural killer cells, and macrophages, were repaired after treatment with venetoclax in patients with CLL. Of note, these repairs remained following the covariate adjustment for treatment responses at 30 days after treatment.

Having a deeper understanding of the interaction between cancer cells and the immune system will allow further development of treatment strategies to implement in clinical practice, especially for patients with B-cell malignancies regarding T-cell engaging therapy, Hernandez-Ilizaliturri concludes.