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.
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.
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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.
- 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]