Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.
Publication/Presentation Date
9-1-2017
Abstract
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated protein CD79B.
Volume
7
Issue
9
First Page
1018
Last Page
1029
ISSN
2159-8290
Published In/Presented At
Grommes, C., Pastore, A., Palaskas, N., Tang, S. S., Campos, C., Schartz, D., Codega, P., Nichol, D., Clark, O., Hsieh, W. Y., Rohle, D., Rosenblum, M., Viale, A., Tabar, V. S., Brennan, C. W., Gavrilovic, I. T., Kaley, T. J., Nolan, C. P., Omuro, A., Pentsova, E., … Mellinghoff, I. K. (2017). Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer discovery, 7(9), 1018–1029. https://doi.org/10.1158/2159-8290.CD-17-0613
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
28619981
Department(s)
Administration and Leadership
Document Type
Article