A Review of the Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies

Overview

Journal J Adv Pract Oncol

Date 2021 Jun 14

PMID 34123480

Citations 5

Authors

Donald C Moore

Daniel Thompson

Affiliations

Soon will be listed here.

Abstract

The B-cell receptor signaling pathway plays an integral role in the proliferation and survival of malignant B cells. Targeting the B-cell receptor pathway via the inhibition of Bruton tyrosine kinase (BTK) has evolved the treatment of a variety of B-cell malignancies, including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia. Currently, there are three BTK inhibitors approved by the U.S. Food and Drug Administration: ibrutinib, acalabrutinib, and zanubrutinib. This article reviews the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions, and implications for advanced practitioners of BTK inhibitors in the treatment of B-cell malignancies.

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References

Iberri D, Kwong B, Stevens L, Coutre S, Kim J, Sabile J . Ibrutinib-associated rash: a single-centre experience of clinicopathological features and management. Br J Haematol. 2016; 180(1):164-166. DOI: 10.1111/bjh.14302. View

Woyach J, Ruppert A, Heerema N, Zhao W, Booth A, Ding W . Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. N Engl J Med. 2018; 379(26):2517-2528. PMC: 6325637. DOI: 10.1056/NEJMoa1812836. View

Borge M, Almejun M, Podaza E, Colado A, Fernandez Grecco H, Cabrejo M . Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages. Haematologica. 2015; 100(4):e140-2. PMC: 4380736. DOI: 10.3324/haematol.2014.119669. View

Stephens D, Byrd J . How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia. Blood. 2019; 133(12):1298-1307. PMC: 6428663. DOI: 10.1182/blood-2018-11-846808. View

Byrd J, Brown J, OBrien S, Barrientos J, Kay N, Reddy N . Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014; 371(3):213-23. PMC: 4134521. DOI: 10.1056/NEJMoa1400376. View

Rule S, Jurczak W, Jerkeman M, Rusconi C, Trneny M, Offner F . Ibrutinib versus temsirolimus: 3-year follow-up of patients with previously treated mantle cell lymphoma from the phase 3, international, randomized, open-label RAY study. Leukemia. 2018; 32(8):1799-1803. PMC: 6087720. DOI: 10.1038/s41375-018-0023-2. View

Kohrt H, Sagiv-Barfi I, Rafiq S, Herman S, Butchar J, Cheney C . Ibrutinib antagonizes rituximab-dependent NK cell-mediated cytotoxicity. Blood. 2014; 123(12):1957-60. PMC: 3962169. DOI: 10.1182/blood-2014-01-547869. View

Dimopoulos M, Tedeschi A, Trotman J, Garcia-Sanz R, MacDonald D, Leblond V . Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia. N Engl J Med. 2018; 378(25):2399-2410. DOI: 10.1056/NEJMoa1802917. View

Noy A, de Vos S, Thieblemont C, Martin P, Flowers C, Morschhauser F . Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017; 129(16):2224-2232. PMC: 5399483. DOI: 10.1182/blood-2016-10-747345. View

10.

Munir T, Brown J, OBrien S, Barrientos J, Barr P, Reddy N . Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Am J Hematol. 2019; 94(12):1353-1363. PMC: 6899718. DOI: 10.1002/ajh.25638. View

11.

Dubovsky J, Beckwith K, Natarajan G, Woyach J, Jaglowski S, Zhong Y . Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013; 122(15):2539-49. PMC: 3795457. DOI: 10.1182/blood-2013-06-507947. View

12.

Treon S, Tripsas C, Meid K, Warren D, Varma G, Green R . Ibrutinib in previously treated Waldenström's macroglobulinemia. N Engl J Med. 2015; 372(15):1430-40. DOI: 10.1056/NEJMoa1501548. View

13.

Sharman J, Egyed M, Jurczak W, Skarbnik A, Pagel J, Flinn I . Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020; 395(10232):1278-1291. PMC: 8151619. DOI: 10.1016/S0140-6736(20)30262-2. View

14.

Wang M, Rule S, Zinzani P, Goy A, Casasnovas O, Smith S . Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2017; 391(10121):659-667. PMC: 7864374. DOI: 10.1016/S0140-6736(17)33108-2. View

15.

Wang M, Rule S, Martin P, Goy A, Auer R, Kahl B . Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013; 369(6):507-16. PMC: 4513941. DOI: 10.1056/NEJMoa1306220. View

16.

Kenkre V, Kahl B . The future of B-cell lymphoma therapy: the B-cell receptor and its downstream pathways. Curr Hematol Malig Rep. 2012; 7(3):216-20. DOI: 10.1007/s11899-012-0127-0. View

17.

Liu J, Fitzgerald M, Berndt M, Jackson C, Gartner T . Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo. Blood. 2006; 108(8):2596-603. PMC: 1895591. DOI: 10.1182/blood-2006-01-011817. View

18.

Shanafelt T, Wang X, Kay N, Hanson C, OBrien S, Barrientos J . Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. N Engl J Med. 2019; 381(5):432-443. PMC: 6908306. DOI: 10.1056/NEJMoa1817073. View

19.

Burger J, Barr P, Robak T, Owen C, Ghia P, Tedeschi A . Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia. 2019; 34(3):787-798. PMC: 7214263. DOI: 10.1038/s41375-019-0602-x. View

20.

Coutre S, Byrd J, Hillmen P, Barrientos J, Barr P, Devereux S . Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies. Blood Adv. 2019; 3(12):1799-1807. PMC: 6595265. DOI: 10.1182/bloodadvances.2018028761. View