No increased bleeding events in patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma treated with idelalisib

Abstract

The advent of novel B-cell receptor pathway targeting agents like ibrutinib dramatically changed management of B-cell malignancies. However, with concomitant anticoagulation (AC) and antiplatelet (AP) therapy, ibrutinib is associated with increased bleeding. This post hoc analysis aimed to determine the role of AC/AP therapy in patients with idelalisib-treated B-cell malignancies and to establish if it contributes to increased bleeding events. Data from two idelalisib trials (rituximab ± idelalisib in chronic lymphocytic leukemia [CLL] and idelalisib monotherapy in indolent non-Hodgkin lymphoma [iNHL]) were analyzed. Antithrombotic therapy was common (36%–63%), with comparable bleeding incidence across treatment groups (14%–19%; p = 0.56). Bleeding events of grade ≥3 occurred in 0.9% and 3.2% of the idelalisib-treated CLL and iNHL cohorts, respectively. Our findings demonstrate no increase in bleeding events with simultaneous AC/AP treatment and idelalisib use. Hemorrhagic risk is prevalent in these patients and an important consideration when evaluating available treatment options.

ClinicalTrials.gov identifiers: NCT01539512 and NCT01282424

Keywords:

• Hemorrhage
• thrombocytopenia
• PI3K inhibitor
• antiplatelet
• anticoagulant

Acknowledgments

We thank the patients who participated in these studies, their family members, the investigators, and the clinical research staff from the study centers. Medical writing and editorial assistance for the development of this manuscript was provided by C4 MedSolutions, LLC (Yardley, PA), a CHC Group company; Percolation Communications LLC (Annandale, NJ); and AlphaScientia (San Francisco, CA).

Author contributions

JCB designed the analysis, analyzed and interpreted data, and wrote the manuscript; PH, GS, JS, SS, PG, and JMP provided patients, collected data, and critically reviewed the manuscript at each draft; OG, GX, and SS designed the analysis, analyzed and interpreted data, and critically reviewed the manuscript at each draft. BR interpreted data, wrote and edited sections of the manuscript, and critically reviewed the manuscript. PB interpreted data and critically reviewed and edited the manuscript. All authors approved the manuscript for submission.

Disclosure statement

Jacqueline C. Barrientos: Institutional research funding from AbbVie and Acerta; advisory board consulting from AbbVie, Acerta, Genentech, Gilead Sciences, and Sandoz; and medical education honoraria from Janssen.

Peter Hillmen: Honoraria and institutional research funding from AbbVie, Gilead Sciences, Inc, Janssen, Novartis, Pharmacyclics, and Roche.

Gilles Salles: Research funding from Roche/Genentech; consultant or advisory role with Celgene, Gilead Sciences, Inc, Janssen Pharmaceuticals, Novartis, Amgen, AbbVie, Autolus, Epizyme, Karyopharm, Morphosys, Servier, Takeda, Genmab, and Roche/Genentech; honoraria from Amgen and Roche/Genentech; reimbursement of travel, accommodations, and expenses from Roche Genentech.

Jeff Sharman: Research funding from AbbVie, AstraZeneca, Genentech, Gilead Sciences, Inc, Pharmacyclics, TG Therapeutics; and consulting fees from AbbVie, AstraZeneca, Bayer, Genentech, Pharmacyclics, TG Therapeutics, and Verastem.

Stephan Stilgenbauer: Honoraria; consulting or advisory role; research funding; and travel, accommodations, and expenses from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Gilead Sciences, Inc, GlaxoSmithKline, Janssen, Mundipharma, Novartis, Pharmacyclics, Roche, and Sanofi.

Paolo Ghia: Consulting or advisory role for AbbVie, Adaptive Biotechnologies, ArQule, BeiGene, Dynamo, Gilead Sciences, Inc, Janssen, MEI, Pharmacyclics, Roche, and Sunesis; speaker’s bureau for Gilead Sciences, Inc; and research funding from AbbVie, Celgene/Juno, Gilead Sciences, Inc, Janssen, and Novartis.

John M. Pagel: Institutional research funding and advisory board consulting from Pharmacyclics and Gilead Sciences, Inc.

Oksana Gurtovaya, Guan Xing, Bianca Ruzicka, Sanatan Shreay, and Pankaj Bhargava are employees of Gilead Sciences, Inc. (Foster City, CA, USA)

Additional information

Funding

The study reported in this publication was supported by the Clinical and Translational Science Center at Weill Cornell Medicine of the National Center for Advancing Translational Sciences under Award number UL1-TR-002384. JCB has received institutional research funding and has served on an advisory board for AbbVie and Gilead Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This study was supported by Gilead Sciences, Inc. Medical writing and editorial assistance for the development of this manuscript was funded by Gilead Sciences, Inc.