Incidence of major bleeding in patients with chronic lymphocytic leukemia receiving ibrutinib and therapeutic anticoagulation

Increased rates of clinically significant bleeding have been reported with ibrutinib, however, limited data is available on the risk when given with concomitant therapeutic anticoagulation. We analyzed the incidence of major bleeding in 64 patient exposures that received ibrutinib with concomitant therapeutic anticoagulation. Major bleeding was observed in 5/64 (8%) patient exposures. The highest incidence was observed with rivaroxaban (3/17, 18%), followed by apixaban (2/35, 6%). No major bleeding events were seen with enoxaparin (n = 10). A total of 38% of patient exposures received a concomitant antiplatelet agent along with therapeutic anticoagulation. Among these patients, one (4%) experienced a fatal hemorrhage while taking ibrutinib, apixaban, and clopidogrel concomitantly. Our retrospective study observed a higher rate of major hemorrhage with combined DOAC with ibrutinib than historically reported with ibrutinib alone. This combination may be associated with increased risk of major bleeding and further prospective studies evaluating this risk are necessary.