Incidence, Type, and Management of Venous and Arterial Thrombosis during Ibrutinib Treatment

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.3148-3148
• Main Authors: Kander, Elizabeth, Zhao, Qiuhong, Wiczer, Tracy, Byrd, John C., Woyach, Jennifer A., Awan, Farrukh T., Rogers, Kerry A., Wang, Tzu-Fei
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-110556

Ibrutinib is an irreversible inhibitor of BTK in the B-cell receptor signaling cascade and is widely used to treat chronic lymphocytic leukemia (CLL) and other B-cell malignancies. Ibrutinib also inhibits the tyrosine kinase Tec in platelets, which may be one of the mechanisms of its bleeding toxicity. This makes concomitant use of anticoagulation (AC) or antiplatelet agents challenging, which is a common delimma as many patients taking ibrutinib are elderly and have increased risks of venous and arterial thromboses. The incidence of thrombosis in patients taking ibrutinib is unknown, and we hypothesized that the risk of thrombosis may be reduced during ibrutinib treatment. Therefore, we conducted a single-institution retrospective cohort study to determine the incidence and type of both arterial and venous thromboses during ibrutinib treatment and their management. We reviewed medical records of all patients treated with ibrutinib for a hematological malignancy at the Ohio State University between 6/1/2010 and 3/31/2016. Baseline patient and disease characteristics were captured at time of starting ibrutinib. All thrombotic events occurring at any time during treatment with ibrutinib and within three days of its discontinuation were recorded. Time to thrombosis was calculated from the date of starting ibrutinib to the date of thrombosis or censored at the last assessment date, treating discontinuation of ibrutinib or death prior to thrombosis as competing risks. The cumulative incidence of thrombosis was estimated and the Fine and Gray regression models accounting for competing riskes were used to examine the association between patient characteristics and risk of thrombosis. The cohort included 565 patients. Median age was 65 (range 23->89) years and 70.3% (397/565) were men. The majority of patients had CLL (73.6%, 416/565). Other diagnoses included mantle cell lymphoma (9.9%, 56/565), indolent B-cell malignancies (8.1%, 46/565), and aggressive lymphomas (8.3%, 47/565). Median number of prior treatments was 3 (range 0-18) and 6.5% (37/565) of patients were treatment naïve. Prior to ibrutinib, 144 of 565 patients (25.5%) had a history of thrombosis. Sixty-four (11.3%, 64/565) patients had only venous thromboses, 66 (11.7% 66/565) had only arterial thromboses, and 14 patients had both. Concurrently with ibrutinib, 193 (34.2%) patients received antiplatelet agents, 16 (2.8%) patients received AC, and 31 (5.5%) patients received both. Total ibrutinib exposu