Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.

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 CenterFollow
• 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.

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