CLL Coverage from Every Angle

Selecting Initial Therapy for CLL: Renewed Focus on Minimal Residual Disease

By: Meg Barbor, MPH
Posted: Tuesday, December 22, 2020

In the front-line treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma, a renewed focus has been placed on minimal residual disease (MRD; also known as measurable residual disease) as a treatment endpoint, according to William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston. Since MRD correlates with clinical outcomes, it is a particularly useful endpoint when assessing survival with combination therapies.

At the 2020 NCCN Annual Congress on Hematologic Malignancies, Dr. Wierda discussed front-line therapy options in CLL and explained how the goals of treatment are changing in the treatment of this malignancy, particularly in regard to eliminating chemoimmunotherapy and replacing it with more effective combinations of small-molecule inhibitors. Highlights from his presentation were published in JNCCN–Journal of the National Comprehensive Cancer Network.

“We have more and more effective treatments available, and we’re learning how to better use those drugs together,” he commented. “We’re expecting to see very long remissions and treatment-free intervals with these new drug combinations, and I’m optimistic about the prospect of curing many of these patients.”

Bruton’s tyrosine kinase (BTK) inhibitors such as ibrutinib and acalabrutinib have demonstrated superiority over chemoimmunotherapy in numerous clinical trials, but remissions with BTK inhibitors were not deep. However, B-cell lymphoma 2 (BCL2) inhibitors such as venetoclax (and new combinations of BCL2 and BTK inhibitors) have led to much deeper remissions as well as high rates of undetectable MRD in patients with CLL. 

Dr. Wierda noted that individual patient characteristics should always be considered when selecting first-line treatment in CLL. He recommends BTK inhibitor–based therapy for patients with 17p deletions. However, for those without 17p deletions, age and comorbidities should be taken into account. “If they’re able to get back and forth to the doctor and have a mutated immunoglobulin gene, I’m interested in BCL2-based therapy.”

Disclosure: For Dr. Wierda’s disclosures, visit

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