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Haematologica. 2017 Oct;102(10):1796-1805. doi: 10.3324/haematol.2017.171041. Epub 2017 Jul 27.

Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials.

Author information

1
Dana-Farber Cancer Institute, Boston, MA, USA jbrown2@partners.org.
2
Division of Cardiovascular Medicine and Cardio-Oncology Program Vanderbilt School of Medicine, Nashville, TN, USA.
3
Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, CA, USA.
4
Università Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele, Milano, Italy.
5
CA Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds, UK.
6
Hôpital Avicenne, AP-HP, UMR Paris13/INSERM U978, Bobigny, France.
7
Mayo Clinic, Rochester, MN, USA.
8
Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.
9
Department of Haematology, Plymouth University Medical School, Plymouth, UK.
10
Moores UCSD Cancer Center, San Diego, CA, USA.
11
Stanford University School of Medicine and Stanford Cancer Institute, Stanford, CA, USA.
12
Hôpital Haut-Lévêque, Bordeaux, Pessac, France.
13
Department I of Internal Medicine and German CLL Study Group, University of Cologne, Germany.
14
Azienda Ospedaliera Niguarda Cà Granda, Milano, Italy.
15
Medical University of Vienna, Austria.
16
Department of Medicine III, Klinikum der Ludwig-Maximilians-Universität München, Campus Grosshadern, Germany.
17
Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
18
Janssen Research & Development, High Wycombe, UK.
19
Janssen Research & Development, LLC, Raritan, NJ, USA.
20
Janssen Research & Development, LLC, Leiden, the Netherlands.
21
Pharmacyclics, Sunnyvale, CA, USA.
22
Leukemia Department, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Abstract

The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize AF with ibrutinib and its management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4% (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence: 13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65 years or over were independent risk factors for AF. Multiple AF events were more common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most (85.7%) patients with AF did not discontinue ibrutinib, and more than half received common anticoagulant/antiplatelet medications on study. Low-grade bleeds were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib, 2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset, these results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation (clinicaltrials.gov identifier: 01578707, 01722487, 01611090, 01646021).

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01578707 NCT01722487 NCT01611090 NCT01646021.

PMID:
28751558
PMCID:
PMC5622864
DOI:
10.3324/haematol.2017.171041
[Indexed for MEDLINE]
Free PMC Article

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