The majority of adverse events (AEs) were Grade 1 or 2 in severity, with the most common AEs attributed to ibrutinib being diarrhea, infections and fatigue. Only 7 percent of patients irrespective of relationship experienced an AE leading to treatment discontinuation. Grade 3-4 hematological toxicities were infrequent, with neutropenia (16 percent), thrombocytopenia (11 percent) and anemia (10 percent) as the most frequent hematological AEs reported.
Data from this study were presented at the annual meeting of the American Society of Hematology in December 2012, the European Hematology Association annual meeting in June 2013 and are being presented at the 12th International Conference on Malignant Lymphoma in Lugano, Switzerland this week.
Study DesignThe Phase 2, open-label, multicenter study was designed to determine the safety and efficacy of ibrutinib in patients with relapsed or refractory MCL. The primary endpoint of the study was overall response rate. Secondary endpoints included: duration of response, progression free survival, overall survival and frequency and severity of adverse events.
The study enrolled patients with a confirmed diagnosis of relapsed or refractory MCL at 18 sites internationally, and 86 percent of patients had intermediate or high-risk MCL. Study participants received a 560mg daily oral dose of ibrutinib monotherapy and were treated into two cohorts based on prior exposure to bortezomib – either no prior bortezomib (n=63) or prior bortezomib (n=48). Overall, patients had received a median of three prior therapies.About Mantle Cell LymphomaMCL, a B-cell malignancy, is an aggressive type of B-cell non-Hodgkin lymphoma (NHL) that usually occurs in older adults. The disease typically begins in the lymph nodes but can spread to other tissues, such as bone marrow and liver. Ibrutinib targets the B-cell receptor pathway an important pathway in malignant B-cell growth and proliferation. In the United States there are approximately 5,000 new cases of MCL each year. About IbrutinibIbrutinib was designed to specifically target and selectively inhibit an enzyme called Bruton tyrosine kinase (BTK). BTK is a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel —regulation of apoptosis, cell adhesion, and cell migration and homing. 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 six Phase 3 trials have been initiated with ibrutinib and a total of 30 trials are currently registered on www.clinicaltrials.gov. Janssen Biotech, Inc. and Pharmacyclics entered a collaboration and license agreement in December 2011 to co-develop and co-commercialize ibrutinib. About PharmacyclicsPharmacyclics ® 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 expertise, develop our products in a rapid, cost-efficient manner and pursue commercialization and/or development with partners when and where appropriate. Presently, Pharmacyclics has two 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.