Retrospective Data Show Zanubrutinib May Less AFib Burden in Real-World CLL

Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who developed atrial fibrillation (AFib) experienced significantly higher rates of cardiovascular and health care resource utilization (HCRU) burden, according to data from a real-world retrospective analysis presented at the 2026 ASCO Annual Meeting, which also showed zanubrutinib (Brukinsa) was associated with lower rates of these burdens.¹

In the primary analysis, investigators identified 233,362 adult patients with newly diagnosed CLL/SLL from the US Symphony Health database, and 13.1% developed AFib within 1 year of diagnosis. Patients who developed AFib (n = 30,518) experienced cardiovascular burdens like stroke (14.3%), bleeding (27.9%), and heart failure (54.5%). Rates of stroke, bleeding, and heart failure in those who did not develop AFib (n = 202,844) were 8.9%, 19.1%, and 18.9%, respectively. These 3 cardiovascular burden rates resulted in a significant difference in burdens between each group (P < .001).

Moreover, patients who received frontline zanubrutinb and developed AFib (n = 1864) experienced lower rates of stroke (4.8%), bleeding (17.4%), and heart failure (39.6%) compared to those who developed AFib and received frontline acalabrutinib (n = 711; Calquence) or ibrutinib (n = 2387; Imbruvica). Patients who received frontline acalabrutinib and had AFib experienced stroke, bleeding, and heart failure at rates of 9.4%, 21.5%, and 45.6%, respectively; these respective rates were 12.2%, 27.4%, and 50.9% for patients who received ibrutinib and had AFib.

Additionally, a significantly greater proportion of patients with CLL/SLL and AFib also used outpatient, inpatient, and other medical/hospital services within 1 year of CLL/SLL diagnosis compared with those without AFib (P < .0001).

“[These] findings highlight a significant real-world cardiovascular and HCRU burden incurred by patients with CLL/SLL and AFib,” Michael G. Fradley, MD, and coauthors wrote in a poster presentation of the data “Exploratory analyses suggest first-line zanubrutinib offers potentially favorable outcomes over other BTK inhibitors in lessening AFib and related clinical and HCRU complications.”

Fradley is a section chief of Consultative Cardiology, medical director of the Thalheimer Center for Cardio-Oncology, and an associate professor of clinical medicine (cardiovascular medicine), all at the University of Pennsylvania Medicine in Philadelphia.

How was the real-world analysis evaluating AFib and BTK inhibitors in CLL designed?

Investigators of the study sought to expand upon the lack of available real-world data for the clinical and economic impact of CLL/SLL-associated AFib.

Data included in the retrospective study spanned from January 1, 2014, through August 31, 2024, with follow-up through August 31, 2025. The study included patients in the US Symphony Health database who were at least 18 years of age, had newly diagnosed CLL/SLL, and had at least 1 documented medical or pharmacy encounter within 30 days of the index date.

The primary end point of the study was to assess the impact of AFib on both cardiovascular outcomes, defined as stroke, bleeding, and heart failure, and HCRU within 1 year of CLL/SLL diagnosis. The impact of CLL-associated AFib on cardiovascular outcomes and HCRU with patients who received frontline zanubrutinib, acalabrutinib, and ibrutinib was the exploratory end point of the analysis.

Baseline characteristics revealed that patients who developed AFib had a median age of 72 years (interquartile range [IQR], 69-75) at index and were mostly male (65.9%). Most patients in this subgroup were above the age 65 (90.7%) and non-Hispanic White (67.7%). Cardiovascular burdens experienced at baseline for patients in this subgroup broke down as AFib (64.5%), heart failure (27.9%), bleeding (10.9%), and stroke (7.0%).

Patients who received zanubrutinib had a median age of 73 years (IQR, 66-78) and were also mostly non-Hispanic White (65.7%), male (60.8%), and over the age of 65 (78.5%). Patients in this group showed cardiovascular burdens such as AFib, stroke, bleeding, and heart failure at respective rates of 8.5%, 2%, 4.1%, and 5.8% within 1 year prior to index.

What additional data were found in the analysis?

Regarding HCRU, the outpatient visit utilization within 1 year of CLL/SLL diagnosis was elevated for the AFib group, with a mean of 16.2 visits (standard deviation [SD], 15.2) vs 11.2 visits (SD, 12.8) for the group without AFib. Additionally, a median of 12 outpatient visits (IQR, 5-22) vs 10 outpatient visits (IQR, 3-15) were shown for AFib and without AFib groups, respectively. At least 1 outpatient visit was experienced by 95.2% of patients in the AFib group compared with 91.4% in the without AFib group.

Similarly, at least 1 inpatient admission occurred in 54.9% of patients in the AFib group vs 91.4% in those without AFib. Mean inpatient visits for each of the respective arms were 1.8 visits (SD, 3.1) and 0.6 visits (SD, 1.9), in addition to a median of 1 (IQR, 0-2) and 0 (IQR, 0-0) inpatient visits, respectively.

Other medical or hospital services were utilized at a median of 4 instances (IQR, 1-12) and 2 instances (IQR, 0-6) for patients in AFib and without AFib groups, respectively.

Patients who were at least 65 years of age who developed AFib (n = 27,668) or did not develop AFib (n = 139,657) experienced stroke (AFib, 14.6%; no AFib, 10.3%), bleeding (28%; 19.4%), and heart failure (55.8%; 22.9%) at rates with similar differences to cohorts in the primary analysis.

Notably, HCRU burdens were significantly higher among older patients with AFib vs those without across all services (P < .0001).

Investigators noted that these findings align with prior clinical evidence that characterized differential cardiac safety profiles across BTK inhibitors in CLL.²

References

1. Fradley M, Addison D, Fu Q, et al. Real-world impact of atrial fibrillation on cardiovascular outcomes and healthcare resource utilization in patients with chronic lymphocytic leukemia.
2. Mohan A, et al. Impact of atrial fibrillation on cardiovascular and economic outcomes in patients with chronic lymphocytic leukemia. Presented at: 63rd ASH Annual Meeting; December 11-14, 2021; Atlanta, GA.