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, 2014; Published: August 31st, 2014;

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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 to: Octavian 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. 

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