Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials
Jennifer R. Brown,Javid Moslehi,Susan O'Brien,Paolo Ghia,Peter Hillmen,Florence Cymbalista,Tait D. Shanafelt,Graeme Fraser,Simon Rule,Thomas J. Kipps,Steven Coutre,Marie Sarah Dilhuydy,Paula Cramer,Alessandra Tedeschi,Ulrich Jaeger,Martin Dreyling,John C. Byrd,Angela Howes,Michael J. Todd,Jessica Vermeulen,Danelle F. James,Fong Clow,Lori Styles,Rudy Valentino,Mark Wildgust,Michelle Mahler,Jan A. Burger +26 more
Reads0
Chats0
TLDR
The results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation, and the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset.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).read more
Citations
More filters
Journal ArticleDOI
2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS).
Alexander R. Lyon,Teresa López-Fernández,Liam Couch,Riccardo Asteggiano,Marianne C. Aznar,Jutta Bergler-Klein,Giuseppe Boriani,Daniela Cardinale,Raul Cordoba,Bernard Cosyns,D Cutter,Evandro de Azambuja,W. De Boer,Susan Dent,Dimitrios Farmakis,Sofie Gevaert,Diana A. Gorog,A. Herrmann,Daniel J. Lenihan,Javid Moslehi,Brenda Moura,Sonja S Salinger,R. Stephens,Thomas M. Suter,Sebastian Szmit,Juan Tamargo,Paaladinesh Thavendiranathan,Carlo G. Tocchetti,P. Van Der Meer,Helena J H van der Pal +29 more
Journal ArticleDOI
Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma
Talha Munir,Jennifer R. Brown,Susan O'Brien,Jacqueline C. Barrientos,Paul M. Barr,Nishitha Reddy,Steven Coutre,Constantine S. Tam,Stephen P. Mulligan,Ulrich Jaeger,Thomas J. Kipps,Carol Moreno,Marco Montillo,Jan A. Burger,John C. Byrd,Peter Hillmen,Sandra Dai,Anita Szoke,James P. Dean,Jennifer A. Woyach +19 more
TL;DR: The robust efficacy of single‐agent ibrutinib over ofatumumab in patients with relapsed/refractory CLL/SLL irrespective of high‐risk clinical or genomic features, with no unexpected AEs is confirmed.
Journal ArticleDOI
A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study.
Constantine S. Tam,Stephen Opat,Shirley D'Sa,Wojciech Jurczak,Hui Peng Lee,Gavin Cull,Gavin Cull,Roger G. Owen,Paula Marlton,Paula Marlton,Björn E. Wahlin,Ramón García Sanz,Helen McCarthy,Stephen P. Mulligan,Alessandra Tedeschi,Jorge J. Castillo,Jarosław Czyż,Carlos Fernández de Larrea,David Belada,Edward N. Libby,Jeffrey Matous,Marina Motta,Tanya Siddiqi,Monica Tani,Marek Trneny,Monique C. Minnema,Christian Buske,Veronique Leblond,Judith Trotman,Judith Trotman,Wai Y. Chan,Jingjing Schneider,Sunhee Ro,Aileen Cohen,Jane Huang,Meletios A. Dimopoulos +35 more
TL;DR: Zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity, which demonstrate that zanubRutinIB and ibrut inib are highly effective in the treatment of WM.
Journal ArticleDOI
Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial.
John C. Byrd,Peter Hillmen,Paolo Ghia,Arnon P. Kater,Asher Chanan-Khan,Richard R. Furman,Susan O'Brien,Mustafa Nuri Yenerel,Árpád Illés,Neil E. Kay,José A. García-Marco,Anthony R. Mato,Javier Pinilla-Ibarz,John F. Seymour,Stéphane Leprêtre,Stephan Stilgenbauer,Tadeusz Robak,Wayne Rothbaum,Raquel Izumi,Ahmed Hamdy,Priti Patel,Kara Higgins,Sophia Sohoni,Wojciech Jurczak +23 more
TL;DR: Among Bruton's tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutanib, which is hypothesized to improve continuous therapy tolerability as mentioned in this paper.
Journal ArticleDOI
Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study
Inhye E. Ahn,Mohammed Farooqui,Xin Tian,Janet Valdez,Clare Sun,Susan Soto,Jennifer Lotter,Stephanie Housel,Maryalice Stetler-Stevenson,Constance M. Yuan,Irina Maric,Katherine R. Calvo,Pia Nierman,Thomas E. Hughes,Nakhle S. Saba,Gerald E. Marti,Stefania Pittaluga,Sarah E. M. Herman,Carsten Utoft Niemann,Lone Bredo Pedersen,Christian H. Geisler,Richard W. Childs,Georg Aue,Adrian Wiestner +23 more
TL;DR: Long-term administration of ibrutinib was well tolerated and provided durable disease control for most patients, and no event occurred in TN-CLL.
References
More filters
Journal ArticleDOI
A Proportional Hazards Model for the Subdistribution of a Competing Risk
Jason P. Fine,Robert Gray +1 more
TL;DR: This article proposes methods for combining estimates of the cause-specific hazard functions under the proportional hazards formulation, but these methods do not allow the analyst to directly assess the effect of a covariate on the marginal probability function.
Journal ArticleDOI
2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society
Craig T. January,L. Samuel Wann,Joseph S. Alpert,Hugh Calkins,Joaquin E. Cigarroa,Joseph C. Cleveland,Jamie B. Conti,Patrick T. Ellinor,Michael D. Ezekowitz,Michael E. Field,Katherine T. Murray,Ralph L. Sacco,William G. Stevenson,Patrick J. Tchou,Cynthia M. Tracy,Clyde W. Yancy +15 more
TL;DR: This document summarizes current research, plans, and recommendations for future research, as well as providing a history of the field and some of the techniques used, currently in use, at the National Institutes of Health.
Journal ArticleDOI
Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.
TL;DR: In this article, a simple stroke risk stratifi cation schema, based on a risk factor approach, provides some improvement in predictive value for TE over the CHADS 2 schema, with low event rates in low-risk subjects and only a small proportion of subjects into the intermediate-risk category.
Journal ArticleDOI
Guidelines for the management of atrial fibrillation The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC)
A. John Camm,Paulus Kirchhof,Irene Savelieva,Isabelle C. Van Gelder,Gerhard Hindricks,Ottavio Alfieri,Johan De Sutter,Andreas Goette,Stefan H. Hohloser,Piotr Ponikowski,Frans H. Rutten +10 more
TL;DR: Estimates of expected health outcomes for larger societies are included, where data exist, and the level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to pre-defined scales.
Journal ArticleDOI
Impact of Atrial Fibrillation on the Risk of Death The Framingham Heart Study
Emelia J. Benjamin,Philip A. Wolf,Ralph B. D'Agostino,Halit Silbershatz,William B. Kannel,Daniel Levy +5 more
TL;DR: There was a significant AF-sex interaction: AF diminished the female advantage in survival and AF remained significantly associated with excess mortality, with about a doubling of mortality in both sexes in subjects free of valvular heart disease and preexisting cardiovascular disease.
Related Papers (5)
Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia
Jan A. Burger,Alessandra Tedeschi,Paul M. Barr,Tadeusz Robak,Carolyn Owen,Paolo Ghia,Osnat Bairey,Peter Hillmen,Nancy L. Bartlett,Jianyong Li,David Simpson,Sebastian Grosicki,Stephen Devereux,Helen McCarthy,Steven Coutre,Hang Quach,Gianluca Gaidano,Zvenyslava Maslyak,Don A. Stevens,Ann Janssens,Fritz Offner,Jiří Mayer,Michael O'Dwyer,Andrzej Hellmann,Anna Schuh,Tanya Siddiqi,Aaron Polliack,Constantine S. Tam,Deepali Suri,Mei Cheng,Fong Clow,Lori Styles,Danelle F. James,Thomas J. Kipps +33 more
Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.
John C. Byrd,Jennifer R. Brown,Susan O'Brien,Jacqueline C. Barrientos,Neil E. Kay,Nishitha Reddy,Steven Coutre,Constantine S. Tam,Stephen P. Mulligan,Ulrich Jaeger,S Devereux,Paul M. Barr,Richard R. Furman,Thomas J. Kipps,Florence Cymbalista,Christopher Pocock,Patrick Thornton,Federico Caligaris-Cappio,Tadeusz Robak,Julio Delgado,Stephen J. Schuster,Marco Montillo,Anna Schuh,S. de Vos,Devinder Gill,Adrian Bloor,Claire Dearden,Carol Moreno,Jeffrey Jones,Alvina D. Chu,Maria Fardis,Jesse McGreivy,Fong Clow,Danelle F. James,Peter Hillmen +34 more
Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia
John C. Byrd,Richard R. Furman,Steven Coutre,Ian W. Flinn,Jan A. Burger,Kristie A. Blum,Barbara Grant,Jeff P. Sharman,Morton Coleman,William G. Wierda,Jeffrey A. Jones,Weiqiang Zhao,Nyla A. Heerema,Amy J. Johnson,Juthamas Sukbuntherng,Betty Y. Chang,Fong Clow,Eric Hedrick,Joseph J. Buggy,Danelle F. James,Susan O'Brien +20 more
Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL
Jennifer A. Woyach,Amy S. Ruppert,Nyla A. Heerema,Weiqiang Zhao,Allison M Booth,Wei Ding,Nancy L. Bartlett,Danielle M. Brander,Paul M. Barr,Kerry A. Rogers,Sameer A. Parikh,Steven Coutre,Arti Hurria,Jennifer R. Brown,Gerard Lozanski,James S. Blachly,Hatice Gulcin Ozer,Brittny Major-Elechi,Briant Fruth,Sreenivasa Nattam,Richard A. Larson,Harry P. Erba,Mark R. Litzow,Carolyn Owen,Charles S. Kuzma,Jeremy S. Abramson,Richard F. Little,Scott E. Smith,Richard Stone,Sumithra J. Mandrekar,John C. Byrd +30 more
Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia
John C. Byrd,Bonnie K. Harrington,Susan O'Brien,Jeffrey A. Jones,Anna Schuh,S Devereux,Jorge M. Chaves,William G. Wierda,Farrukh T. Awan,Jennifer R. Brown,Peter Hillmen,Deborah M. Stephens,Paolo Ghia,Jacqueline C. Barrientos,John M. Pagel,Jennifer A. Woyach,Dave Johnson,Jane Huang,Xiaolin Wang,Allard Kaptein,Brian J. Lannutti,Todd Covey,Maria Fardis,Jesse McGreivy,Ahmed Hamdy,Wayne Rothbaum,Raquel Izumi,Thomas G. Diacovo,Amy J. Johnson,Richard R. Furman +29 more