Ibrutinib (Imbruvica)

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General information

Class/mechanism: Irreversible inhibitor of Bruton's tyrosine kinase (BTK), which is an enzyme that participates in the B-cell receptor (BCR) signal cascade and cytokine receptor pathways. BCR signaling is believed to promote cell proliferation, adhesion, and survival in B-cell malignancies. Inhibition of BTK interferes with the processes above, as well as B-cell chemotaxis and trafficking.[1][2][3] [4]
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]

Resistance mechanisms

  1. Woyach JA, Furman RR, Liu TM, Ozer HG, Zapatka M, Ruppert AS, Xue L, Li DH, Steggerda SM, Versele M, Dave SS, Zhang J, Yilmaz AS, Jaglowski SM, Blum KA, Lozanski A, Lozanski G, James DF, Barrientos JC, Lichter P, Stilgenbauer S, Buggy JJ, Chang BY, Johnson AJ, Byrd JC. Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib. N Engl J Med. 2014 Jun 12;370(24):2286-94. Epub 2014 May 28. link to original article PubMed

Significant side effects


  1. Review: Leong DP, Caron F, Hillis C, Duan A, Healey JS, Fraser G, Siegal D. The risk of atrial fibrillation with ibrutinib use: a systematic review and meta-analysis. Blood. 2016 Jul 7;128(1):138-40. Epub 2016 May 31. link to original article PubMed
  2. Dickerson T, Wiczer T, Waller A, Philippon J, Porter K, Haddad D, Guha A, Rogers KA, Bhat S, Byrd JC, Woyach JA, Awan F, Addison D. Hypertension and incident cardiovascular events following ibrutinib initiation. Blood. 2019 Nov 28;134(22):1919-1928. link to original article PubMed


  1. Review: Caron F, Leong DP, Hillis C, Fraser G, Siegal D. Current understanding of bleeding with ibrutinib use: a systematic review and meta-analysis. Blood Adv. 2017 May 9;1(12):772-778. eCollection 2017 May 9. Review. link to original article link to PMC article PubMed


  1. Review: Tillman BF, Pauff JM, Satyanarayana G, Talbott M, Warner JL. Systematic review of infectious events with the Bruton tyrosine kinase inhibitor ibrutinib in the treatment of hematologic malignancies. Eur J Haematol. 2018 Apr;100(4):325-334. Epub 2018 Feb 6. link to original article PubMed
  2. Ghez D, Calleja A, Protin C, Baron M, Ledoux MP, Damaj G, Dupont M, Dreyfus B, Ferrant E, Herbaux C, Laribi K, Le Calloch R, Malphettes M, Paul F, Souchet L, Truchan-Graczyk M, Delavigne K, Dartigeas C, Ysebaert L; on behalf on the French Innovative Leukemia Organization (FILO) CLL group. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib. Blood. 2018 Apr 26;131(17):1955-1959. Epub 2018 Feb 1. link to original article PubMed

Diseases for which it is established (work in progress)

Diseases for which it is used

Patient drug information

History of changes in FDA indication

Chronic graft versus host disease (cGVHD)

Chronic lymphocytic leukemia

Mantle cell lymphoma - WITHDRAWN

  • 2013-11-13: Accelerated approval for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. (Based on PCYC-1104-CA)
    • 2023-05-18: Accelerated approval for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy withdrawn.

Marginal zone lymphoma - WITHDRAWN

Waldenström macroglobulinemia

History of changes in EMA indication

  • 2014-10-21: Initial authorization

History of changes in Health Canada indication

  • 2015-07-28: Initial notice of compliance with conditions
  • 2017-09-12: Conditions were met

History of changes in PMDA indication

Also known as

  • Code names: CRA-032765, PCI-32765
  • Brand names: Ibrunib, Ibrutix, Imbruvica, Lucibru