Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Dan Rohle, Marc Rosenblum, Agnes Viale, Viviane S Tabar, Cameron W Brennan, Igor T Gavrilovic, Thomas J Kaley, Craig P Nolan, Antonio Omuro, Elena Pentsova, Alissa A Thomas, Elina Tsyvkin, Ariela Noy, M Lia Palomba, Paul Hamlin, Craig S Sauter, Craig H Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C Lallana, Vaios Hatzoglou, Anne S Reiner, Philip H Gutin, Jason T Huse, Katherine S Panageas, Thomas G Graeber, Nikolaus Schultz, Lisa M DeAngelis, Ingo K Mellinghoff
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...
September 2017: Cancer Discovery