Changes in primary and secondary hemostasis in patients with CLL treated with venetoclax and ibrutinib

Rebecka Svanberg, Sisse Rye Ostrowski, Kazem Nasserinejad, Sabina Kersting, Johan A. Dobber, Mattias Mattson, Hoa T.T. Tran, Mark David Levin, Rogier Mous, Arnon P. Kater, Carsten U. Niemann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Bleeding is a common adverse event following ibrutinib monotherapy. However, it remains unclear how hemostasis is affected by venetoclax in combination with ibrutinib. Here we investigated hemostasis in patients with chronic lymphocytic leukemia (CLL) at baseline, during ibrutinib monotherapy, and during venetoclax and ibrutinib combination therapy or venetoclax monotherapy. Primary hemostasis, assessed by Multiplate using adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor agonist peptide (TRAP-6), was impaired in all CLL patients at baseline, remained unchanged upon ibrutinib monotherapy, and improved significantly following venetoclax added to ibrutinib or as monotherapy. Secondary hemostasis assessed by thromboelastography (TEG) was normal and unchanged throughout treatment. The frequency of clinical bleeding events was the highest during ibrutinib monotherapy, in line with the demonstrated improved primary hemostasis upon addition of venetoclax, thus pointing toward a treatment option for CLL patients with increased bleeding risk.

Original languageEnglish
Pages (from-to)3422-3431
Number of pages10
JournalLeukemia and Lymphoma
Issue number14
Publication statusPublished - 2020

Bibliographical note

Funding Information:
This work was supported the Novo Nordisk Foundation under grant NNF16OC0019302 (C.N.) and the Danish National Research Foundation under Grant 126 (R.S.). AbbVie and Janssen provided study drug and financial support for the clinical trial, had the chance to comment on the paper, but no further influence on the content and did not approve the final manuscript. The authors would like to acknowledge all investigators and patients participating in the clinical trial.

Funding Information:
C.N. received support, consultancy fees or travel grants from Abbvie, Gilead, Janssen, Roche, CSL Behring, Acerta, Genmab, Sunesis and Astra Zeneca outside this work. R.S. received travel grants from Abbvie outside this work. The remaining authors declare no competing financial interests.

Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.


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