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 CitationGrommes, 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.