Dr Cortese on Future Directions for the Multiomic Investigation of Venetoclax in CLL

“Venetoclax works and repairs the immune system to a degree. Venetoclax monotherapy in [a patient with CLL] who’s very sick all the time would be a reasonable option, [although] an unconventional option [in the context of] looking to extend time to next treatment and progression-free survival. [However, it] certainly is an option and something to be aware of for the future and for research purposes, too.”

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 next steps for the multiomic evaluation of venetoclax (Venclexta) activity in patients with chronic lymphocytic leukemia (CLL).

More research in this area is needed, Cortese emphasized. However, Cortese stated that the work that has been done already has identified both germline and somatic mutations that may be clinically relevant in smaller patient subgroups. Notably, study findings in larger cohorts are less influenced by genomic variability, which may affect the reliability of observed results, he explained.

Research efforts at Roswell Park are actively expanding in this area, according to Cortese. He helped design and implement an automatic consent protocol, which allows patients with newly diagnosed CLL the option to contribute to research by donating surplus blood samples—specimens that would otherwise be discarded. This facilitates the development of CAR T cells and enables comprehensive multiomic analyses across a broad patient population, he noted. Although funding for this research remains a challenge, Roswell Park investigators are seeking support through industry partnerships, grants, and collaborative efforts with other institutions to validate these findings.

Venetoclax continues to be a cornerstone of standard-of-care treatment for patients with CLL and appears to exert a restorative effect on immune function, Cortese said. Although venetoclax monotherapy may not be a conventional treatment option for these patients, it may be rational in patients with significant comorbidities or immunologic compromise, although its use must be considered within the context of goals prolong progression-free survival and delay the need for subsequent therapy, he reported. Therefore, venetoclax monotherapy remains an important therapeutic consideration for CLL, particularly in the context of ongoing clinical research, he concluded.