Which Treatment Strategies Work Best in CLL Management?

Scott Huntington, MD, MPH, MSc, spoke with CancerNetwork® about his strategies for selecting the most appropriate therapies for patients with chronic lymphocytic leukemia (CLL). He detailed how relevant molecular factors and patient characteristics may influence the types of usable therapy across different populations.

According to Huntington, 2 primary treatment strategies in CLL management include continuous therapy—often with a Bruton’s tyrosine kinase inhibitor—and fixed-duration therapy, which typically includes a venetoclax (Venclexta) backbone. He stated that patients with lower-risk disease, such as those who are younger, may benefit from fixed-duration therapy and treatment-free intervals that last several years. On the other hand, those who are older and have more competing comorbidities may be candidates to receive continuous therapy and other strategies intended to ease administration and minimize visits to the clinic.

Huntington is an associate professor of Internal Medicine (Hematology) at Yale School of Medicine and the Medical Director of Yale Cancer Center's Hematology Outpatient Program.

Transcript:

For patients these days, we have 2 strategies. One strategy is continuous therapy with the Bruton's tyrosine kinase inhibitor, and then the other strategy is what we call fixed-duration treatment with a backbone of venetoclax. We are moving towards combining both orally administered therapies, the Bruton's tyrosine kinase inhibitors with the venetoclax, to allow [intravenous]-free, all-oral, fixed-duration treatments. When selecting either continuous or fixed-duration treatment, we think about both molecular factors—what is driving the CLL—and then also patient factors. In terms of molecular features that might lead us to one decision over another—17p status mutation in a TP53 gene, or those that have an unmutated heavy chain—we view those as a little more aggressive. Historical data support often using a continuous approach, at least in the first-line setting. When we think about patients who have lower-risk disease, where they will likely benefit from fixed-duration treatment, and then have treatment-free intervals lasting many years, that's when we often will favor fixed-duration venetoclax-based therapy.

Also, there are patient factors. If a patient is older [and] has competing comorbidities, the therapy might be focused on ease of administration and minimizing the [number] of visits to clinic, and that often favors this continuous kind of single-agent Bruton's tyrosine kinase inhibitor approach. [Alternatively], if you have a patient who is young, having a treatment-free interval with a fixed-duration therapy with venetoclax-based therapy is often favored. Again, in CLL, we think about the actual disease characteristics molecularly. Also, [we consider], “What are the patient's values and desires for their treatment plan?”