Annals of Hematology

, Volume 96, Issue 7, pp 1175–1184 | Cite as

Ibrutinib in CLL: a focus on adverse events, resistance, and novel approaches beyond ibrutinib

  • Varinder KaurEmail author
  • Arjun Swami
Review Article


Bruton’s tyrosine kinase (BTK), a mediator in B cell receptor signaling has been successfully exploited as a therapeutic target in treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Ibrutinib is a BTK inhibitor that has shown excellent efficacy in treatment-naïve, heavily pre-treated, and high-risk CLL/SLL. With remarkable efficacy, good oral bioavailability, and modest adverse events profile, ibrutinib use is likely to continue to increase. As data with ibrutinib use in CLL matures, concerns regarding adverse events and drug resistance have emerged. New insights into mechanisms of ibrutinib resistance in CLL have uncovered potential therapeutic targets. Several promising novel agents are currently in early phases of development for overcoming ibrutinib resistance in CLL/SLL. We provide a comprehensive analysis of emerging adverse events profile of ibrutinib, summarize our current understanding of ibrutinib resistance in CLL, and review promising novel therapeutic tools to overcome this challenge.


Ibrutinib resistance CLL SLL Bruton’s tyrosine kinase inhibition Resistance Novel therapeutic agents 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


This work received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Medicine, Division of Hematology/OncologyUniversity of VirginiaCharlottesvilleUSA
  2. 2.Departement of MedicineGovt. Medical CollegeChandigarhIndia

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