Document Type
Article
Publication 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.
Recommended Citation
Grommes, Christian; Pastore, Alessandro; Palaskas, Nicolaos; Tang, Sarah S.; Campos, Carl; Schartz, Derrek; Codega, Paolo; Nichol, Donna; Clark, Owen; Hsieh, Wan-Ying; Rohle, Dan; Rosenblum, Marc; Viale, Agnes; Tabar, Viviane S.; Brennan, Cameron W.; Gavrilovic, Igor T.; Kaley, Thomas J.; Nolan, Craig P.; Omuro, Antonio; Pentsova, Elena; Thomas, Alissa A.; Tsyvkin, Elina; Noy, Ariela; Palomba, M. Lia; Hamlin, Paul; Sauter, Craig S.; Moskowitz, Craig H.; Wolfe, Julia; Dogan, Ahmet; Won, Minhee; Glass, Jon; Peak, Scott; Lallana, Enrico C.; Hatzoglou, Vaios; Reiner, Anne S.; Gutin, Philip H.; Huse, Jason T.; Panageas, Katherine S.; Graeber, Thomas G.; Schultz, Nikolaus; DeAngelis, Lisa M.; and Mellinghoff, Ingo K., "Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma." (2017). Department of Neurology Faculty Papers. Paper 167.
https://jdc.jefferson.edu/neurologyfp/167
PubMed ID
28619981
Language
English
Comments
This article has been peer reviewed. It is the authors' final version prior to publication in Cancer Discovery, Volume 7, Issue 9, September 2017, Pages 1018-1029.
The published version is available at https://doi.org/10.1158/2159-8290.CD-17-0613. Copyright © American Association for Cancer Research Inc.