Targeting Chronic Lymphocytic Leukemia

Clinical trial results suggest patients with high-risk chronic lymphocytic leukemia may benefit from a combination of two targeted therapeutics.

Patients with high-risk chronic lymphocytic leukemia (CLL) may benefit from a treatment regimen that combines two targeted therapies for a fixed amount of time, according to clinical trial results published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR).

Formerly treated with chemoimmunotherapy, CLL is now usually treated with targeted therapies that work to block the action of proteins that help cancer cells survive. 

A recent clinical trial suggested that combining the targeted therapies ibrutinib (Imbruvica) and venetoclax (Venclexta) may be effective in treating patients with CLL. To avoid or limit toxicities, the targeted therapies were given for a specified period and then stopped, an approach described as “fixed-duration.”

The results were encouraging, but it wasn’t clear if the regimen would be effective against high-risk disease, in which patients’ cancers have certain genetic characteristics that are associated with worse outcomes. 

“Since high-risk genetic features inform treatment selection, understanding the efficacy of fixed-duration ibrutinib plus venetoclax in patients with high-risk CLL is important to determine how this regimen fits in the first-line treatment algorithm for the disease,” said John Allan, MD, an associate professor of clinical medicine at Weill Cornell Medicine and first author of the study. 

In the latest publication, Allan and colleagues reported that patients had similar outcomes to the treatment whether or not their CLL harbored high-risk genetic features, with a 95% response rate in both groups. Additionally, over 95% of patients in both groups were alive 36 months after beginning treatment, and adverse events were similar.

“Previously reported results from the CAPTIVATE study demonstrated deep and durable responses with sustained [progression-free survival] after fixed-duration therapy with ibrutinib plus venetoclax for first-line treatment of CLL,” said Allan. “The current analysis builds upon those results by demonstrating that these clinical outcomes are maintained at these early time points in patients with CLL harboring high-risk genomic features.”

He added that further follow-up will be needed to understand long-term outcomes for these patients.