BTK Inhibitor Selection for CLL/SLL Is Evolving in Community Settings


A retrospective cohort study acalabrutinib and zanubrutinib are being increasingly adopted for the treatment of CLL/SLL in the community setting.

Ira Zackon, MD

Ira Zackon, MD

Findings from a retrospective, observational cohort study showed that treatment patterns for BTK inhibitors administered to patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the community setting have shifted away from ibrutinib (Imbruvica) with the increased adoption of acalabrutinib (Calquence) and zanubrutinib (Brukinsa). The analysis, which examined the relationship between patient demographics, treatment patterns, and social determinants of health in patients with CLL/SLL who received treatment with a BTK inhibitor in the community oncology setting, was presented during the 28th International Congress on Hematologic Malignancies.

Among the 2082 patients identified for this retrospective study who initiated BTK inhibitor treatment between January 1, 2020, and April 30, 2023, 55.7% of patients received acalabrutinib (n = 1,159) without a subsequent BTK inhibitor; 30.2% were administered ibrutinib (n = 628) without a subsequent BTK inhibitor; and 5.4% received zanubrutinib (n = 113) without a subsequent BTK inhibitor. The study population also included patients who switched from ibrutinib to acalabrutinib (n = 82), patients who switched from acalabrutinib to ibrutinib (n = 62), and patients who switched from acalabrutinib to zanubrutinib (n = 38).

When treatment type was broken down by year, investigators noted the shift in community practice patterns away from ibrutinib. Patients treated in 2020 (n = 597; 28.7%) received ibrutinib only (55.4%); acalabrutinib only (34.2%); zanubrutinib only (0.2%); ibrutinib then acalabrutinib (6.9%); acalabrutinib then ibrutinib (2.2%); or acalabrutinib then zanubrutinib (1.2%).

Ibrutinib usage subsequently decreased among all patients treated in 2021 (n = 663), 2022 (n = 616) and 2023 (n = 206), whereas usage of acalabrutinib and zanubrutinib increased during this time fram. In 2023, 6.8% of patients received ibrutinib only; 58.3% received acalabrutinib only; 28.6% received zanubrutinib only; 2.9% switched from acalabrutinib to ibrutinib; and 3.4% switched from acalabrutinib to zanubrutinib.

The retrospective cohort study included adult patients diagnosed with CLL/SLL whose initial BTK inhibitor treatment commenced between January 1, 2020, and April 30, 2023. The study excluded patients who did not have a follow-up visit post–BTK inhibitor initiation; had unavailable electronic health record data; had multiple BTK inhibitors prescribed simultaneously at treatment initiation; were enrolled on another clinical trial; or underwent treatment for a different primary cancer after commencing treatment with their BTK inhibitor.

Patient data were collected from structured fields of The US Oncology Network’s electronic health care record—iKnowMed (iKM)—and the Financial Data Warehouse, which were both linked to other external databases to assess social determinants of health. The Neighborhood Atlas® provided area deprivation index (ADI) scores based on patients' socioeconomic factors, and the US Department of Agriculture's rural/urban commuting area code database contributed rural/urban classifications. Insurance status was based on information from the Financial Data Warehouse; notably, Medicaid served as an indicator of low socioeconomic status.

Investigators stratified patients into treatment sequence subgroups based on their immediate subsequent treatment after their first BTK inhibitor. Descriptive analyses were conducted to assess patient characteristics and social determinants of health measures to identify any significant associations.

In the overall treatment group, the median age was 73 years (range, 21 to 90+) and the majority of patients enrolled were male (61.9%) and White (73.5%). Rai stages included stage 0 (19.5%); stage I and II (26.5%); stage III and IV (27.1%); and no staging information (26.9%). Additionally, 16.0% of patients had an ECOG performance status (PS) of 0; 28.0% had an ECOG PS status of 1; and 5.9% had an ECOG status of 2 or higher. Notably, ECOG PS data were unavailable for 50.1% of patients.

Moreover, 84.0% of patients (82.4% [lower limit] to 85.6% [upper limit]) were classified as urban, 6.6% (5.6%-7.7%) were classified as rural, and 9.4% (8.2%-10.8%) had no information. Additionally, 17.3% of patients (15.7%-19.0%) had low socioeconomic status at the state level, and 6.0% (5.0%-7.1%) had low socioeconomic status at the national level. Regarding payor distribution, 3.5% of patients (2.8%-4.4%) had Medicaid; 42.1% (40.0%-44.3%) had Medicare; 24.4% (22.6%-26.3%) had managed Medicare; 10.9% (9.6%-12.3%) had commercial insurance; and 19.1% (17.5%-20.9%) had no insurance information available.

Additional data showed that a statistical difference was observed in treatment regimen groups categorized by rural/urban status (P < .01). However, no statistical differences were observed concerning state ADI (P = .52), national ADI (P = .36), or Medicaid insurance coverage vs all other coverage (P = .18).

“Similarities in social determinants of health measures across the treatment sequence subgroups suggest that patients’ socioeconomic status and Medicaid utilization do not influence prescribing patterns,” Ira Zackon, MD, senior medical director of Ontada in Boston Massachusetts, and colleagues, wrote in a poster presentation of the data. “Differences across treatment subgroups regarding rural/urban status warrant further consideration.”

Zackon et al. wrote that some strengths of the study included the utilization of real-world clinical data sourced from patients, representing a substantial portion of patients with cancer across the United States. Additionally, they noted the iKM electronic health record has been implemented across all practices within The US Oncology Network, allowing for a homogenized dataset.

However, investigators also noted limitations in the study, including the possibility of errors of omission and commission within the dataset; the lack of a specified minimum follow-up time; and the use of an intent-to-treat approach assuming full adherence to prescribed oral therapies, which could not be independently verified solely through structured data.

“Further real-world investigations and longitudinal follow-up are needed to examine the impacts of social determinants of health on treatment choice, treatment switching, reasons for switching, and outcomes among users of BTK inhibitors,” study authors concluded.


Zackon I, Andorsky DJ, Wilson TW, et al. Recent patterns of care with BTK inhibitors and distribution of social determinants of health among patients with chronic lymphocytic leukemia/small lymphocytic lymphoma in the US community setting. Presented at: 28th International Congress on Hematologic Malignancies; February 29 to March 3, 2024. Miami, FL.

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