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Full-Text Articles in Medicine and Health Sciences
Resistance Mechanisms For The Bruton's Tyrosine Kinase Inhibitor Ibrutinib, J. A. Woyach, R. R. Furman, T. M. Liu, H. G. Ozer, M. Zapatka, A. S. Ruppert, L. Xue, D. H. H. Li, J. C. Barrientos, J. C. Byrd, +15 Additional Authors
Resistance Mechanisms For The Bruton's Tyrosine Kinase Inhibitor Ibrutinib, J. A. Woyach, R. R. Furman, T. M. Liu, H. G. Ozer, M. Zapatka, A. S. Ruppert, L. Xue, D. H. H. Li, J. C. Barrientos, J. C. Byrd, +15 Additional Authors
Journal Articles
BACKGROUND Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL). Resistance to irreversible kinase inhibitors and resistance associated with BTK inhibition have not been characterized. Although only a small proportion of patients have had a relapse during ibrutinib therapy, an understanding of resistance mechanisms is important. We evaluated patients with relapsed disease to identify mutations that may mediate ibrutinib resistance. METHODS We performed whole-exome sequencing at baseline and the time of relapse on samples from six patients with acquired resistance to ibrutinib therapy. We then performed functional analysis of identified mutations. …
Idelalisib And Rituximab In Relapsed Chronic Lymphocytic Leukemia, R. R. Furman, J. P. Sharman, S. E. Coutre, B. D. Cheson, J. M. Pagel, P. Hillmen, J. C. Barrientos, A. D. Zelenetz, T. J. Kipps, S. M. O'Brien, +17 Additional Authors
Idelalisib And Rituximab In Relapsed Chronic Lymphocytic Leukemia, R. R. Furman, J. P. Sharman, S. E. Coutre, B. D. Cheson, J. M. Pagel, P. Hillmen, J. C. Barrientos, A. D. Zelenetz, T. J. Kipps, S. M. O'Brien, +17 Additional Authors
Journal Articles
BackgroundPatients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies with acceptable side-effect profiles are needed for this patient population. MethodsIn this multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab plus placebo. We randomly assigned 220 patients with decreased renal function, previous therapy-induced myelosuppression, or major coexisting illnesses to receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice daily. …
Ibrutinib Versus Ofatumumab In Previously Treated Chronic Lymphoid Leukemia, J. C. Byrd, J. R. Brown, S. O'Brien, J. C. Barrientos, N. E. Kay, N. M. Reddy, S. Coutre, C. S. Tam, S. P. Mulligan, P. Hillmen, +25 Additional Authors
Ibrutinib Versus Ofatumumab In Previously Treated Chronic Lymphoid Leukemia, J. C. Byrd, J. R. Brown, S. O'Brien, J. C. Barrientos, N. E. Kay, N. M. Reddy, S. Coutre, C. S. Tam, S. P. Mulligan, P. Hillmen, +25 Additional Authors
Journal Articles
Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response …