Ibrutinib therapy carries a significantly higher risk of atrial fibrillation/flutter and all-grade bleeding compared with other treatments, according to a study published in the Clinical Lymphoma, Myeloma & Leukemia.1

Ibrutinib is a kinase inhibitor indicated for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), and Waldenstrom macroglobulinemia. Clinical trials demonstrate that ibrutinib therapy may cause hemorrhage and atrial fibrillation/flutter, though the precise risk of these adverse events is undetermined.

Investigators analyzed data from more than 1500 patients with CLL/SLL or mantle cell lymphoma included in 4 randomized clinical trials. Of those, 758 received ibrutinib with or without chemoimmunotherapy, and 751 received ofatumumab, chlorambucil, bendamustine plus rituximab, or temsirolimus.

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Ibrutinib treatment was associated with a significantly higher incidence of serious atrial fibrillation/flutter (relative risk [RR], 3.80, 95% CI, 1.56-9.29; P = .003), all-grade atrial fibrillation/flutter (RR, 8.81; 95% CI, 2.70-28.75; P = .0003), and all-grade bleeding (RR, 2.93; 95% CI, 1.14- 7.52; P = .03). There was no difference in the rates of major bleeding (RR, 1.72; 95% CI, 0.95-3.11; P = .07).

Disease type, number of prior lines of therapy, dose, and ibrutinib treatment duration were not associated with differences in the incidence of serious arrhythmia or major bleeding.

RELATED: Ibrutinib Linked With Favorable Survival, High Response Rate in CLL

The authors note that this study is limited by not all trials reporting underlying cardiovascular comorbidities or coagulopathy, potentially affecting the risk of atrial fibrillation/flutter and bleeding.

The findings suggest that clinicians should carefully consider the risk-to-benefit ratio of anticoagulation among patients with hematologic malignancies treated with ibrutinib.                    


  1. Yun S, Vincelette ND, Acharya U, Abraham I. Risk of atrial fibrillation and bleeding diathesis associated with ibrutinib treatment: a systematic review and pooled-analysis of four randomized controlled trials. Clin Lymphoma Myeloma Leuk. 2016 Sep 19. doi: 10.1016/j.clml.2016.09.010 [Epub ahead of print]