Patients with chronic lymphocytic leukemia (CLL) who are treated with ibrutinib may have a higher incidence of atrial fibrillation (AF) than previously thought, according to a retrospective analysis published in Annals of Hematology.

Using the Mayo Clinic CLL Database, the study researchers retrospectively identified patients with CLL who received ibrutinib at Mayo Clinic between October 2012 and November 2018.

Among the 298 patients identified from the database, 51 (17%) developed treatment-emergent AF, which included 39 patients with incident AF and 12 with recurrent AF. Among the 21 patients with a history of AF, nearly half — 9 patients — did not develop AF during treatment with ibrutinib.

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The estimated cumulative incidence of treatment-emergent AF differed between patients with incident AF and patients with recurrent AF. Those with incident AF had an estimated cumulative incidence of 9% at 1 year, 13% at 2 years, 16% at 3 years, while those with recurrent AF had an estimated cumulative incidence of 43% at 1 year, 48% at 2 years, and 56% at 3 years.

The study authors wrote that the risk of treatment-emergent AF at 2 years was approximately 16%, “which is significantly higher than that reported in ibrutinib registration trials.”

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According to a multivariable analysis, history of AF was independently associated with a more than 3-fold increased risk of developing AF (hazard ratio [HR], 3.5; 95% CI, 1.4–8.7; P =.0072), as was a history of heart failure (HR, 3.4; 95% CI, 1.5–7.7; P =.0028).

Multivariable analyses also revealed that treatment-emergent AF was significantly associated with shorter event-free survival (HR, 2.0; 95% CI, 1.1–3.8; P =.02) and overall survival (HR, 3.2; 95% CI, 1.6–6.3; P =.001).


Archibald WJ, Rabe KG, Kabat BF, et al. Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib: Risk prediction, management, and clinical outcomes [published online June 1, 2020]. Ann Hematol. doi: 10.1007/s00277-020-04094-3