Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Real-world data show that covalent BTK inhibitors were the most commonly prescribed first-line therapy in older adults with CLL, and most patients are not receiving all recommended biomarker tests before starting treatment.
Who Performed the Research and Where Was it Presented:
Dr. Paul Hampel from Mayo Clinic and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) is the most common leukemia in US adults, and the treatment landscape has changed substantially in the last decade. Although much of the research on CLL / SLL is conducted at academic medical centers, many patients are seen in community practices across the country. For this study, researchers used a national database to take a broad look at 1) what treatments were being prescribed as first-line therapies and 2) how biomarker testing is being used for patients with CLL / SLL in the US.
Methods and Participants:
This was a retrospective study using de-identified Medicare data. The study included patients who were diagnosed with CLL / SLL at ≥65 years of age and started first-line treatment between 2020 and 2024.
Results:
- A total of 21,008 patients were included in the study with a median age of 76 years at the start of their first treatment.
- 43% of patients were 65-74 years of age; 43% were 75-84 years of age, and 14% were ≥85 years of age.
- Covalent Bruton tyrosine kinase inhibitors (BTKi) were the most common first-line treatment (41%), with 15% of patients receiving ibrutinib, 16% receiving acalabrutinib, and 10% receiving zanubrutinib.
- Patients who received covalent BTKi monotherapy were more likely to be older and have other ongoing health conditions.
- Use of covalent BTKi increased from 41% in 2020 to 48% in 2024, largely driven by increased use of zanubrutinib.
- 11% of patients received a BCL2 inhibitor (venetoclax) plus an anti-CD20 monoclonal antibody (rituximab, obinutuzumab).
- Combinations of a covalent BTKi + an anti-CD20 monoclonal antibody (6%) or a covalent BTKi + a BCL2 inhibitor (1%) were less common.
- 13% of patients received chemoimmunotherapy (most commonly bendamustine plus rituximab)
- 22% of patients received only an anti-CD20 monoclonal antibody (rituximab, obinutuzumab).
- Most patients had some type of biomarker testing performed, which helps understand how the disease might respond to certain treatments and what the patient’s prognosis might look like.
- Most patients had FISH testing performed (69%), but few were tested for TP53 mutation (12%) or IGHV status (28%).
- Only 16% of patients on chemoimmunotherapy had received IGHV testing, which is a critical test because patients with unmutated IGHV do not respond well to chemoimmunotherapy.
Conclusions:
Covalent BTK inhibitors were the most commonly prescribed first-line therapy in older adults with CLL. This is perhaps not surprising given that older patients usually have several other underlying health conditions that they are managing, and covalent BTK inhibitors are easy to get started on. Surprisingly, many patients received chemoimmunotherapy or anti-CD20 monoclonal antibody monotherapy, neither of which is a recommended first-line therapy.
Additionally, this study revealed that a substantial proportion of patients with CLL are not receiving all three recommended biomarker tests (FISH, TP53, IGHV) prior to starting treatment. Biomarker testing provides unique genetic results that are key to understanding how aggressive your disease might be, and can help in understanding how your body might react to different medications and thus guide treatment decisions. Both patient education and physician education are important to help bridge this gap. Here at the CLL Society, we provide a Test Before Treat™ handout that explains biomarker testing, which can be shared with your healthcare provider.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Real-world treatment patterns and biomarker utilization among patients aged ≥65 years with CLL / SLL from 2020 to 2024
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