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Management and Outcomes of Atrial Fibrillation in Patients Receiving Ibrutinib for Hematologic Malignancies at a Single Center

Conference Correspondent - Conference Correspondent, ASH 2016 - Chronic Lymphocytic Leukemia

Ibrutinib (ibr) is FDA-approved for chronic lymphocytic leukemia, mantle-cell lymphoma, and Waldenström’s macroglobulinemia. High overall response rates, extended progression-free survival, and an acceptable adverse event profile make ibr an impactful therapy for these malignancies. However, atrial fibrillation (AF) has been identified as a less common but serious adverse effect of ibr, with a reported incidence ranging from 2% to 16% in clinical trials and postmarketing experience, with a pooled rate of 3.3/100 person-years.1 Data regarding the management of AF in this patient population is thus far limited, especially for embolic stroke prevention, which poses a particular clinical challenge as ibr carries an inherent bleeding risk that may be increased by antiplatelet therapy and therapeutic anticoagulation. Wiczer and colleagues report on their experience at Ohio State University on the management and outcomes of a large cohort of patients who developed AF while on ibr therapy.

Patients with hematologic malignancies and incident or recurrent AF while on ibr therapy at the Ohio State University were identified retrospectively. Incident AF was defined as new-onset AF in patients without a history of AF and recurrent AF as an AF event requiring new intervention in patients with a prior history of AF. Out of a total of 582 CLL patients included in the final analysis, 76 patients with incident or recurrent AF were identified, of which 63 patients developed incident AF and 13 patients developed recurrent AF while on ibr. Patients were followed for a median of 4.3 years from the start of ibr and 14.2 months from an AF event. Ninety-three percent of the AF events were grade 1-2 and 7% were grade 3. First-line therapy for AF included rate control for 60 (79%) patients, interventional procedural strategies for 14 (18.4%), and rhythm control for 16 (21.1%). Seven (9.2%) patients required no intervention. Twenty-two (30.5%) patients required a second and 4 (5.5%) required third-line AF management intervention. Among those with a secondary AF management strategy, rhythm control was the most frequently utilized (n = 10; 45.5%). During the AF events, 31 (43.1%) patients continued ibr, 35 (48.6%) temporarily held ibr, 5 (6.9%) discontinued ibr, and 1 patient had the dose reduced. Patients with recurrent AF were less likely to be treated with anticoagulation when compared with patients with incident AF. Seven patients had 9 major bleeding events, and 2 of these patients went on to have a second major bleed. Of the 8 major bleeding events, 3 occurred with concomitant antiplatelet therapy and no patients were on anticoagulation therapy at the time of bleeding. Eighteen (25%) patients developed a total of 25 clinically relevant nonmajor bleeding events (9 grade 1 events, 13 grade 2 events, 2 grade 3 events, and 1 could not be graded). Only 1 potential embolic event occurred in a patient on aspirin 325 mg who developed symptoms consistent with stroke. The authors conclude that the incidence in their CLL patient population on ibr is 7.4/100 person-years, which is a higher incidence than previously reported. AF events in patients treated with ibr are generally manageable and in the majority of cases did not result in drug discontinuation. Clinically relevant bleeding events are common, and caution must be exercised when initiating routine antiplatelet therapy and/or anticoagulation in patients being treated with ibr. Risk of ischemic stroke was low in this patient population, although follow-up was limited. This study validates a history of AF and Framingham Heart Study risk score as significant risk factors for the development of AF while on ibr, and that this risk may be reduced with discontinuation or dose reduction of ibr.

 Wiczer TE, et al. ASH 2016. Abstract 2040. 

  1. Thompson PA, et al. Br J Haematol. 2016;175:462-466.
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Last modified: August 30, 2021