Authors

Christian Grommes, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Alessandro Pastore, Memorial Sloan Kettering Cancer Center
Nicolaos Palaskas, Memorial Sloan Kettering Cancer Center; University of California, Los Angeles
Sarah S. Tang, Memorial Sloan Kettering Cancer Center
Carl Campos, Memorial Sloan Kettering Cancer Center
Derrek Schartz, Memorial Sloan Kettering Cancer Center
Paolo Codega, Memorial Sloan Kettering Cancer Center
Donna Nichol, Memorial Sloan Kettering Cancer Center; Personal Genome Diagnostics, Baltimore
Owen Clark, Memorial Sloan Kettering Cancer Center
Wan-Ying Hsieh, Memorial Sloan Kettering Cancer Center
Dan Rohle, Memorial Sloan Kettering Cancer Center; Roche, Basel, Switzerland
Marc Rosenblum, Memorial Sloan Kettering Cancer Center
Agnes Viale, Memorial Sloan Kettering Cancer Center
Viviane S. Tabar, Memorial Sloan Kettering Cancer Center
Cameron W. Brennan, Memorial Sloan Kettering Cancer Center
Igor T. Gavrilovic, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Thomas J. Kaley, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Craig P. Nolan, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Antonio Omuro, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College; University of Miami
Elena Pentsova, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Alissa A. Thomas, Memorial Sloan Kettering Cancer Center; University of Vermont
Elina Tsyvkin, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Ariela Noy, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
M. Lia Palomba, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Paul Hamlin, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Craig S. Sauter, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Julia Wolfe, Memorial Sloan Kettering Cancer Center
Ahmet Dogan, Memorial Sloan Kettering Cancer
Minhee Won, NRG Oncology Statistics and Data Management Center
Jon Glass, Thomas Jefferson UniversityFollow
Scott Peak, The Permanente Medical Group
Enrico C. Lallana, The Permanente Medical Group
Vaios Hatzoglou, Memorial Sloan Kettering Cancer Center
Anne S. Reiner, Memorial Sloan Kettering Cancer Center
Philip H. Gutin, Memorial Sloan Kettering Cancer Center
Jason T. Huse, Memorial Sloan Kettering Cancer Center; MD Anderson Cancer Center
Katherine S. Panageas, Memorial Sloan Kettering Cancer Center
Thomas G. Graeber, University of California, Los Angeles
Nikolaus Schultz, Memorial Sloan Kettering Cancer Center
Lisa M. DeAngelis, Memorial Sloan Kettering Cancer Center; Weill Cornell Medical College
Ingo K. Mellinghoff, Memorial Sloan Kettering Cancer Center

Document Type

Article

Publication Date

9-1-2017

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.

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.

PubMed ID

28619981

Language

English

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