Navigating Dramatic Changes and Using Novel Therapies in CLL Management

The chronic lymphocytic leukemia (CLL) landscape has “dramatically changed” within the last 15 or 20 years, according to Scott Huntington, MD, MPH, MSc.

In a conversation with CancerNetwork®, Huntington outlined the options that make up the current treatment paradigm in CLL management. He noted that the field has generally shifted away from administering chemotherapy-based approaches, with practices embracing the use of orally available agents like venetoclax (Venclexta) and antibody-based treatments such as rituximab (Rituxan). These novel options, Huntington described, may offer “excellent” quality of life benefits for an extended period.

Given that many patients receive a CLL diagnosis based on incidental observation, Huntington described how active surveillance may help appropriately treat these newly diagnosed patients. In the event of progression or observable symptoms stemming from CLL, Huntington stated that determining the molecular characteristics of one’s disease may help influence treatment decision-making in the first line and subsequent settings.

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:

The way that we approach treatment for CLL has dramatically changed in the last 15 or 20 years. It was a disease that was typically treated with chemotherapy [and] is now treated with novel non–chemotherapy-based therapies, often orally administered targeted therapies such as Bruton’s tyrosine kinase inhibitors, or more recently, a BCL-2 inhibitor named venetoclax. We have shifted away from giving chemotherapy to better tolerated, orally administered therapies, with or without immunotherapy. We also incorporate antibody-based therapies called rituximab or obinutuzumab [Gazyva] for these patients, but what we are able to do is maintain excellent quality of life, oftentimes for more than a decade, for a disease that otherwise has been incurable. Again, these novel therapies can work quite well and lead to great outcomes for our patients.

In terms of sequencing therapy, we think about a patient as [having] newly diagnosed CLL. The first question is, do patients really need treatment at time of diagnosis? Many patients are incidentally discovered to have CLL, and so those patients are managed appropriately with what we call active surveillance. If patients develop progression or symptoms from their CLL, that’s when we would start treatment. To select treatment, we often need the molecular characteristics of the CLL. That helps direct which therapy we will use in the first-line setting, and which therapies will be used subsequently.