Ibrutinib’s off-target mechanism: cause for dose optimization

Sara M. Zimmerman, Cody J. Peer, William D. Figg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Ibrutinib (Imbruvica®, 2013) is a Bruton’s tyrosine kinase (BTK) inhibitor approved for multiple B-cell malignancies and cGVHD. Its treatment is associated with increased risk of cardiac adverse events. Atrial fibrillation is a common cause of therapy discontinuation and interruptions, which have been correlated with shorter progression-free survival in chronic lymphocyte leukemia (CLL) patients. Recently, Xiao et al. identified that ibrutinib-mediated atrial fibrillation is likely due to off-target CSK inhibition. Given promising in vitro and in vivo evidence of maintained biological activity in CLL at lower-than-labeled ibrutinib doses, this elucidated mechanism substantiates the case to investigate alternative dosing schedules. The potential to minimize ibrutinib’s off-target effects while conserving response warrants further discussion and investigation of optimal ibrutinib dosing.

Original languageEnglish
Pages (from-to)529-531
Number of pages3
JournalCancer Biology and Therapy
Issue number10-12
StatePublished - 2021
Externally publishedYes


  • CSK
  • Keywords ibrutinib
  • atrial fibrillation
  • dose optimization


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