Existing users Log In New users Sign up


Ibrutinib: a promising novel therapy for B-cell hematologic malignancies

DISCOVERIES REPORTS (ISSN 2393249X), 2014, September-December issue

CITATION: 

Dumitrascu GR, Bucur O. Ibrutinib: a promising novel therapy for B-cell hematologic malignancies. Discoveries Reports 2014, Sep-Dec; 1(1): e3. DOI: 10.15190/drep.2014.3

Submitted: July 23rd, 2014; Revised: August 29th, 2014; Accepted: August 29th, 2014Published: August 31st, 2014;

 GO BACK to 2014, September-December issue

 GO BACK to DISCOVERIES REPORTS

Ibrutinib: a promising novel therapy for B-cell hematologic malignancies

Georgiana Roxana Dumitrascu (1), Octavian Bucur (2,*)  

(1) "Victor Babes” National Institute of Pathology and Biomedical Sciences, Bucharest, Romania; 
(2) Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA;

*Correspondence toOctavian Bucur, MD, Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA; E-mail: obucur@bidmc.harvard.edu

Abstract

B cell malignancies are hematological disorders that originate from either precursors or mature B cells. Uncontrolled proliferation of B lymphocytes occurs in B cell acute lymphoblastic/chronic lymphocytic leukemia and in both non-Hodgkin and Hodgkin lymphomas. Non-Hodgkin lymphoma is one of the most frequent types of malignancy in the United States, in contrast to Hodgkin lymphoma, and 85% of non-Hodgkin lymphoma originates from the proliferation of B lymphocytes. It is well known that among high toxicity induced by single or combined therapy, the resistance to treatment and frequent relapsed/refractory disease are also real challenges in the treatment of the complex B-cell non-Hodgkin lymphomas. Thus, new strategies for treatment are urgently needed. Ibrutinib (PCI-32765) is a new therapy for hematological malignancies affecting the mature B-cell. Recently approved by FDA for treatment of patients with mantle cell lymphoma and chronic lymphocytic leukemia and also designated by European Medicines Agency as an orphan drug for rare conditions, such as diffuse large B-cell lymphoma and follicular lymphoma, Ibrutinib could be a great strategy for treatment of non-responders to the first-line therapies, with a tremendous potential for elderly patients. Due to the irreversible covalent binding of Ibrutinib with Bruton’s tyrosine kinase (Btk), a great efficacy and less toxicity were reported for small lymphocytic lymphoma, prolymphocytic leukemia, multiple myeloma, hairy cell leukemia, Waldenstrom's macroglobulinemia and marginal zone lymphoma. New insights into Ibrutinib’s mechanisms of action and resistance to therapy may contribute to the development of novel efficacy strategies for personalized therapy of B-cell malignancies and also to a better control of the severe adverse reaction

Access full text of the manuscript here: 

References

1. Swerdlow S.H., Campo E., Harris N.L., Jaffe E.S., Pileri S.A., Stein H. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. France: IARC: Lyon. 2008

2. Claudio Agostinelli and Stefano Pileri. Pathobiology of Hodgkin Lymphoma. Mediterr J Hematol Infect Dis. 2014. 6(1):e2014040

3. SEER Cancer Statistics Factsheets: Hodgkin Lymphoma. National Cancer Institute. Accesed at http://seer.cancer.gov/statfacts/html/hodg.html, in August 25, 2014

4. SEER Cancer Statistics Factsheets: Non-Hodgkin Lymphoma. National Cancer Institute. Bethesda, MD,  Accesed at http://seer.cancer.gov/statfacts/ html/nhl.html, in July 16th 2014

5. Vinjamaram S, Estrada-Garcia DA, Hernandez-Ilizaliturri FJ.  Non-Hodgkin Lymphoma. Medscape. Accesed at http://emedicine.medscape.com/article/ 203399-overview#aw2aab6b2b2 , in July 16th 2014

6. U.S. Food and Drug Administration (FDA). Ibrutinib. Accesed at http://www.fda.gov/drugs/information ondrugs/approveddrugs/ucm374857.htm, in May 23th, 2014

7. U.S. Food and Drug Administration (FDA). Ibrutinib (IMBRUVICA). Accesed at http://www.fda.gov/ drugs/informationondrugs/approveddrugs/ucm385878.htm, in May 23th, 2014

8. European Medicines Agency EU/3/13/1203. Accesed at http://www.ema.europa.eu/ema/ index.jsp ?curl=pages/medicines/human/orphans/2013/12/human_orphan_001282.jsp&mid=WC0b01ac058001d12b, in May 23th, 2014 

9. European Medicines Agency EU/3/13/1212. Accesed at http://www.ema.europa.eu/ema/index.jsp?curl =pages/medicines/human/orphans/2014/01/human_orphan_001297.jsp&mid=WC0b01ac058001d12b, in May 23th, 2014

10. Brown JR. PCI-32765, the First BTK (Bruton’s Tyrosine Kinase) Inhibitor in Clinical Trials. Curr Hematol Malig Rep. 2013. 8(1): 1–6.

11. O'Brien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014. 15(1):48-58.

12. Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013. 31(1):88-94. 

13. Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010. 107(29):13075-80

14. Ortutay C, Nore BF, Vihinen M, Smith CI. Phylogeny of Tec family kinases identification of a premetazoan origin of Btk, Bmx, Itk, Tec, Txk, and the Btk regulator SH3BP5. Adv Genet. 2008. 64:51-80

15. Mohamed AJ, Yu L, Bäckesjö CM, Vargas L, Faryal R, Aints A, et al. Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev. 2009. 228(1):58-73.

16. de Rooij MF1, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, Pals ST, Spaargaren M.The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012. 119(11):2590-4.

17. Hendriks RW, Yuvaraj S, Kil LP. Targeting Bruton's tyrosine kinase in B cell malignancies. Nat Rev Cancer. 2014. 14(4):219-32.

18. Aalipour A, Advani RH. Bruton tyrosine kinase inhibitors: a promising novel targeted treatment for B cell lymphomas. Br J Haematol. 2013.163(4):436-43

19. Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y et al. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013. 122(15):2539-49.

20. U.S. Food and Drug Administration (FDA). Ibrutinib - Highlights of Prescribing Information. Accesed at http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203147s000lbl.pdf, in May 23th, 2014

21. Juggernaut CLL/MCL Drug, Ibrutinib, En Route to FDA Approval. Pharmacy Practice News. 2013:40

22. Fowler N, Davis E. Targeting B-cell receptor signaling: changing the paradigm. Hematology Am Soc Hematol Educ Program. 2013. 2013:553-60. 

23. Woyach JA, Furman RR, Liu TM, Ozer HG, Zapatka M, Ruppert AS et al. Resistance Nechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib. N Engl J Med. 2014. [Epub ahead of print]

24. Furman RR, Cheng S, Lu P, Setty M, Perez AR, Guo A, et al. Ibrutinib Resistance in Chronic Lymphocytic Leukemia. N Engl J Med. 2014. Epub ahead of print

25. Stancu AL, Smith MR, Almasan A. New agents for the treatment of lymphoid leukemia and lymphoma: focus on recent FDA approvals. Discoveries. 2014. 2(1):e14

26. ClinicalTrials.gov. U.S. National Institutes of Health. Ibrutinib. Accesed at https://clinicaltrials.gov/ct2/ results?term=Ibrutinib&Search=Search, in July 15th, 2014

27. Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013. 369(6):507-16

28. Treon SP, Tripsas CK, Yang G, Cao Y, Xu L, Hunter Z et al. A Prospective Multicenter Study Of The Bruton’s Tyrosine Kinase Inhibitor Ibrutinib In Patients With Relapsed Or Refractory Waldenstrom’s Macroglobulinemia. 2013.55th ASH Annual Meeting and Exposition, New Orleans, LA.

29. Herman SE, Niemann CU, Farooqui M, Jones J, Mustafa RZ, Lipsky A, et al.  Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study. Leukemia. 2014. 

News & Events Latest news from Discoveries Reports

  • 2015 | Indexed by Google Scholar

    All our published articles are now indexed by Google Scholar! First citations to articles published in Discoveries Reports are included! Search for the article's title (recommended) or the authors:

    Google Scholar Search
  • 2014 | Discoveries Reports

    DOIs (Digital Object Identifiers) are now assigned to all our published manuscripts in Discoveries Reports. DOI uniquely identifies an article and is provided by CrossRef.

    CrossRef
  • 2014 | Manuscript Submission

    Submit your manuscript FREE, FAST and EASY ! (in less than 1 minute)
    There are NO fees for the manucript submission or publishing of the accepted manuscripts.

    read more
  • 2014 | DISCOVERIES REPORTS

    We are now ACCEPTING MANUSCRIPTS for DISCOVERIES REPORTS, publishing inovative and important research findings from all areas related to Medicine, Biology and Chemistry. We are also accepting experimental articles that validate/invalidate highly used reagents in current publications (ex. antibodies) and selected articles presenting negative data with impact and of wide scientific interest ...

    read more
Member Login
Free Registration Click here to sign up
Copyright © 2013 Applied Systems. All Rights Reserved.