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

• Published in: Haematologica (Roma) Vol. 102; no. 10; pp. 1796 - 1805
• Main Authors: Brown, Jennifer R., Moslehi, Javid, O’Brien, Susan, Ghia, Paolo, Hillmen, Peter, Cymbalista, Florence, Shanafelt, Tait D., Fraser, Graeme, Rule, Simon, Kipps, Thomas J., Coutre, Steven, Dilhuydy, Marie-Sarah, Cramer, Paula, Tedeschi, Alessandra, Jaeger, Ulrich, Dreyling, Martin, Byrd, John C., Howes, Angela, Todd, Michael, Vermeulen, Jessica, James, Danelle F., Clow, Fong, Styles, Lori, Valentino, Rudy, Wildgust, Mark, Mahler, Michelle, Burger, Jan A.
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.10.2017
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Atrial Fibrillation - diagnosis; Atrial Fibrillation - epidemiology; Atrial Fibrillation - etiology; Atrial Fibrillation - therapy; Disease Management; Female; Follow-Up Studies; Hemorrhage - etiology; Humans; Incidence; Life Sciences; Male; Middle Aged; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Randomized Controlled Trials as Topic; Risk Factors; Time Factors
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2017.171041

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 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 ( ).