The Evolution of Treatment Patterns for Chronic Lymphocytic Leukemia (CLL): Trends in the US Community Oncology Setting from 2015 to 2024
Authors: Su Zhaohui , Herms Lisa , Paulus Jessica , Robert Nicholas , Zackon Ira 
Published: December 2024

Background: The treatment landscape for chronic lymphocytic leukemia (CLL) has evolved significantly over the last decade, driven by advancements in targeted therapies and a deeper understanding of the disease's molecular underpinnings. Historically, chemoimmunotherapy (CIT) regimens, combining chemotherapy with monoclonal antibodies, were the mainstay of treatment. However, the advent of novel agents like Bruton tyrosine kinase (BTK) inhibitors and B-cell lymphoma 2 (BCL-2) inhibitors has revolutionized patient management and paved the way for a new era in CLL management. We therefore sought to characterize the changing landscape of treatment from 2015 to 2024 in a large real-world dataset of patients with CLL treated in a US community oncology setting.
Methods: This was a retrospective observational study using structured electronic health records data from within The US Oncology Network and selected non-Network practices, which covers a nationally representative network of over 2,700 providers and more than 1 million patients seen annually in community-based oncology practices. The analysis included patients with diagnosis of CLL between 1/1/2015 to 6/30/2024. The index date was the date of initial diagnosis or first visit after the initial diagnosis if the initial diagnosis date was not documented in the structured data. Patient demographics at index were descriptively summarized overall and by index year. A multivariable logistic regression was employed to model the likelihood of receiving each drug class of interest, while adjusting for the index year and patient characteristics.
Results: A total of 7,893 patients with CLL were identified. The majority (64%) were male, with 74% being White, 7% Black, 5% of other races, and 14% missing race information. The mean age at the index date was 70 years (standard deviation [SD] 11 years). The proportion of patients treated with BCL2-inhibitors as an initial regimen increased from 4.8% in 2015 to 25.6% in 2024. Similarly, the proportion of patients treated with BTK inhibitors as the first regimen increased from 36.6% for patients with index year 2015 to 60.2% for patients with index year 2024. Conversely, the proportion of patients treated with chemotherapy as the first regimen decreased from 43.3% for index year 2015 to 6.8% for index year 2024. There was also a decrease in the use of anti-CD20 monoclonal antibodies as the first regimen, dropping from 54.6% for index year 2015 to 36.8% for index year 2024. Interaction analysis did not indicate any differential time trends in uptake of the novel agents by patient age, sex, or race/ethnicity. Over the study period overall, older patients (≥70 years) were less likely to receive chemotherapies (p=0.013) and anti-CD20 monoclonal antibodies (p&lt;0.0001), and more likely to receive BTK inhibitors (p=0.0002) and BCL-2 inhibitors (p&lt;0.0001) than younger patients (&lt;60 years). Female patients were also less likely to receive chemotherapy than male patients (p&lt;0.0001). Treatment patterns for all therapies were otherwise consistent across US census regions, rural and urban areas, ECOG, body mass index (BMI), race and ethnicity categories.
Conclusions: This analysis of initial regimens for the treatment of CLL patients in a community oncology setting during the time since the introduction of BTK inhibitors and subsequent BCL-2 inhibitors describes remarkable changes in treatment patterns. From the years 2015 to 2024, there was a marked increase in the use of these novel agents appearing as the first regimen after diagnosis or first visit, with an even more notable decline in cytotoxic chemotherapy use. The use of anti-CD20 antibodies in these patients also declined concurrently with these changes. It is encouraging that these trends in uptake were consistent across various demographic and geographic subgroups. Overall, the data reflect a broad shift in CLL treatment, with wide adoption of novel agents in the real-world community oncology setting.