(C-221) Atrial Fibrillation and Bleeding in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) on Ibrutinib vs Acalabrutinib: Role of Age, Frailty, and Anticoagulants

Background: Ibrutinib, the first Bruton tyrosine kinase (BTK) inhibitor, is a more effective treatment compared to the previously used chemoimmunotherapy regimens for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), though increases risk of atrial fibrillation and bleeding. The second generation BTK inhibitor, acalabrutinib, showed similar efficacy but an improved safety profile compared to ibrutinib in a phase III trial. It is unclear if older, frailer patients taking anticoagulants also benefit from the improved safety profile of acalabrutinib.

Objectives: To compare the risk of atrial fibrillation and bleeding in real-world clinical care settings between ibrutinib and acalabrutinib users and to evaluate if there was effect modification of treatment effects by age, frailty, and anticoagulant use.

Methods: Using real-world data from 63 United States healthcare organizations in the TriNetX Network, we conducted a 1:1 propensity score matched new user cohort study among patients with CLL/SLL treated with ibrutinib or acalabrutinib. Data contained records from November 21, 2019 to October 23, 2023 and included demographics, health care encounters, diagnoses, and medications. Outcomes included atrial fibrillation and bleeding. Atrial fibrillation was defined using International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes from inpatient or emergency department encounters. Bleeding was a composite outcome of gastrointestinal bleeding and intracranial hemorrhage identified using corresponding ICD-10 diagnosis codes from inpatient encounters. Incidence rates and rate differences (RDs) with corresponding 95% confidence intervals (CIs) were calculated by Poisson regression with robust standard errors.

Results: The incidence rates of atrial fibrillation and bleeding per 100 person-years were higher in ibrutinib users than acalabrutinib users (adjusted RD=-2.95, 95% CI (-5.04, -0.85) and adjusted RD=-1.90, 95% CI (-3.11, -0.69), respectively). Across most subgroups, patients taking acalabrutinib had lower rates of atrial fibrillation and bleeding. Older patients and patients taking anticoagulants had higher rates of atrial fibrillation and bleeding compared to younger patients and patients without anticoagulant use.

Conclusions: Acalabrutinib appears to offer a lower risk of atrial fibrillation and bleeding compared to ibrutinib.