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

Abstract

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.

Keywords:

• Chronic lymphocytic leukemia
• ibrutinib
• anticoagulation
• major bleeding
• direct oral anticoagulant
• enoxaparin

Disclosure statement

The authors report the following conflicts of interest:

Laura M. Roccograndi: nothing to disclose

Alexandra R. Lovell: Oncology Times honoraria for articles written

Alessandra Ferrajoli: Janssen Advisory Board

Philip A. Thompson: received research funding from AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies; advisory board/consultancy: Janssen, AbbVie, Adaptive Biotechnologies, Beigene, Lilly, and Genentech

Jan A. Burger: received research funding from Pharmacyclics LLC and BeiGene; served on the advisory board for Janssen, Gilead, TG Therapeutics, Pharmacyclics LLC, BeiGene, and Novartis

William G. Wierda: received research funding from GSK/Novartis, Abbvie, Genentech, Pharmacyclics LLC, AstraZeneca/Acerta Pharma, Gilead Sciences, Bristol Myers Squibb (Juno & Celgene), KITE Pharma, Sunesis, Miragen, Oncternal Therapeutics, Inc., Cyclacel, Loxo Oncology, Inc./Lilly, Janssen, Xencor

Nitin Jain: received research funding from Pharmacyclics, AbbVie, Genentech, AstraZeneca, BMS, Pfizer, Servier, ADC Therapeutics, Cellectis, Adaptive Biotechnologies, Incyte, Precision Biosciences, Aprea Therapeutics, Fate Therapeutics, Kite/Gilead, Mingsight, Takeda, Medisix, Loxo Oncology, Novalgen, Dialectic Therapeutics, Newave, TransThera Sciences; served on the advisory board for Pharmacyclics, Janssen, AbbVie, Genentech, AstraZeneca, BMS, Adaptive Biotechnologies, Kite/Gilead, Precision Biosciences, Beigene, Cellectis, TG Therapeutics, MEI Pharma, Ipsen, CareDX

Caitlin R. Rausch: nothing to disclose

Additional information

Funding

This research received no funding.