Dr Cortese on the Role of Venetoclax in CLL Immune Synapse Repair

“We normalized our results based on lymphocyte count reduction, evaluating white blood cell count, tumor burden by physical exam, and CT imaging. Although imaging was part of standard care, only approximately half of the patients underwent elective scans. After normalization, immune repair effects remained significant despite covariate adjustment."

Matthew Cortese, MD, MPH, assistant professor, Department of Medicine–Lymphoma, and Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, discusses the 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, further studies with larger patient cohorts are necessary to determine the extent to which venetoclax contributes to immune restoration, Cortese begins. Looking ahead, he suggests that patients with CLL requiring CAR T-cell therapy may benefit from prior treatment with BCL-2 inhibitors in combination with T-cell–engaging therapies to enhance treatment outcomes. He notes that although CAR T-cell therapy has demonstrated efficacy in large B-cell lymphoma, its activity in CLL has been less pronounced. However, opportunities exist to optimize these approaches for CLL, he says.

Specifically, findings from the analysis demonstrated that multiple immune compartments, including T cells, natural killer cells, and macrophages, exhibited repair following treatment with venetoclax in patients with CLL. Notably, these immune modifications remained significant following covariate adjustment for treatment responses at 30 days post-treatment.

A deeper understanding of the interactions between cancer and the immune system will facilitate the development of improved treatment strategies in clinical practice, particularly for B-cell malignancies where T-cell–engaging therapies are under investigation.

Cortese concludes that although further research is needed, identified germline and somatic mutations may have greater relevance in smaller patient cohorts. As cohort size decreases, genetic confusion diminishes, leading to more confident results. Ongoing research will focus on patients receiving standard-of-care venetoclax to further refine these findings.