Study of Mechanism of Action of Ibrutinib in Mantle Cell Lymphoma Published in Blood - Journal of the American Society of Hematology
SUNNYVALE, Calif., Aug. 22, 2013 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq: PCYC) announced today the publication of a study that investigated the mechanism of ibrutinib's anti-tumor effect in patients with mantle cell lymphoma (MCL) in Blood, the most cited peer-reviewed journal in the field of hematology. The article was pre-published online shortly after acceptance in manuscript format as a First Edition Paper.
Response of MCL patients to ibrutinib was noted during early clinical trials to be accompanied by increases in absolute lymphocyte count (ALC) in the peripheral blood. MCL cells typically grow in the lymph nodes and tissues where they receive signals and support that are essential for their survival and growth. In the current paper, Pharmacyclics Vice President of Research, Betty Chang, along with colleagues and collaborators, showed that the lymphocytes, which increase in the peripheral blood during ibrutinib treatment, are MCL cells rather than normal cells. Moreover, the data indicate ibrutinib may directly and potently inhibit MCL cell adhesion and migration in the residing lymph nodes or tissues. This publication illustrates these cells show decreases of markers of activation and growth as treatment continued and nodal responses were observed.
"For the first time, we demonstrate that the increase in lymphocytes in the peripheral blood is due to an egress of MCL cells from tissues, such as the lymph nodes. Following ibrutinib treatment these cells are released in a matter of days into the peripheral blood where they are then quickly cleared systemically. This general mechanism was previously postulated for BCR antagonists in CLL but it is now characterized in detail in MCL showing how ibrutinib can lead to the observed responses," said Betty Chang, Vice President of Research Biology at Pharmacyclics.
About Mantle Cell Lymphoma
MCL is a B-cell malignancy, an aggressive type of B-cell non-Hodgkin lymphoma (NHL) that usually occurs in older adults.i The disease typically begins in the lymph nodes, but can spread to other tissues, such as bone marrow, liver, and spleen.ii Patients typically survive an average of five years.iii There are approximately 5,600 new cases of MCL each year in the G7 (U.S., France, Germany, Italy, Spain, U.K., and Japan) and a prevalence of about 23,000 patients (Decision Resources 2012).
Ibrutinib is an investigational agent designed to provide potent and sustained inhibition of an enzyme called Bruton's tyrosine kinase (BTK). BTK is a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel – regulation of apoptosis, adhesion, and cell migration and homing. Through these multiple signals, BTK regulation helps to direct malignant B-cells to lymphoid tissues, thus allowing access to a micro-environment necessary for survival.
The effectiveness of ibrutinib alone or in combination with other treatments is being studied in several B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Waldenstrom's macroglobulinemia and multiple myeloma. To date, 7 Phase III trials have been initiated with ibrutinib and a total of 31 trials are currently registered on www.clinicaltrials.gov. Janssen and Pharmacyclics entered a collaboration and license agreement in December 2011 to co-develop and co-commercialize ibrutinib.
Pharmacyclics® is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative small-molecule drugs for the treatment of cancer and immune mediated diseases. Our mission and goal is to build a viable biopharmaceutical company that designs, develops and commercializes novel therapies intended to improve quality of life, increase duration of life and resolve serious unmet medical healthcare needs; and to identify promising product candidates based on scientific development and administrational expertise, develop our products in a rapid, cost-efficient manner and pursue commercialization and/or development partners when and where appropriate.
Presently, Pharmacyclics has three product candidates in clinical development and several preclinical molecules in lead optimization. The company is committed to high standards of ethics, scientific rigor, and operational efficiency as it moves each of these programs to viable commercialization.
Pharmacyclics is headquartered in Sunnyvale, California and is listed on NASDAQ under the symbol PCYC. To learn more about how Pharmacyclics advances science to improve human healthcare visit us at http://www.pharmacyclics.com.
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i Cancer.net. "Lymphoma – Non-Hodgkin". http://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes. Accessed April 2013.
ii Know Cancer. "Mantle Cell Lymphoma". Available at: http://www.knowcancer.com/oncology/mantle-cell-lymphoma/. Accessed April 2013.
iii Geisler, C. (2010) "Front-line treatment of mantle cell lymphoma." Haematologica, 95:8:1241-1243. Available at: http://www.haematologica.org/content/95/8/1241.full
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