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Pharmacyclics Announces Data Presentations for Ibrutinib in B-Cell Malignancies
Date:12/10/2013

ted total tissue disease burden. Therefore the majority of tissue shrinkage is attributed to apoptosis of the CLL cells in the tissue. These findings indicate that generally a relatively small fraction of the total tissue CLL cell burden is re-distributed into the blood during ibrutinib therapy, and that a significant amount of drug-induced cell death occurs in tissue compartments.

Oral Abstract #118: Effective Inhibition Of Tumor Microenvironment Interactions In CLL Patients Treated With The BTK Inhibitor Ibrutinib Results In Sustained Inhibition Of Tumor Proliferation and Survival Pathways
Sarah E. M. Herman, PhD, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD

Prior studies have shown that CLL cells in the lymph node and bone marrow microenvironments demonstrate higher levels of BCR and NF-κB signaling as well as increased cell activation and proliferation (Herishanu et al., Blood 2011). This study's goal was to determine the in vivo effect of ibrutinib on tumor cell activation and proliferation in these microenvironmental niches. Analysis of bone marrow from two cycles of treatment shows that ibrutinib effectively inhibits BCR, NF-κB, and ERK signaling. This occurs very quickly as demonstrated in the lymph node and is sustained on treatment as shown in the bone marrow. The strong and sustained reduction in proliferation and activation of CLL cells in the tissue microenvironment suggests that BTK is indeed a central hub mediating the nourishing and protective effects of the tumor microenvironment.

About IMBRUVICA
IMBRUVICA (ibrutinib) is indicated for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. This indication is based on overall response rate (ORR). An improvement in survival or disease-related symptoms has not been established. For more inform
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