Title |
Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma
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Published in |
Cancer Cell, May 2017
|
DOI | 10.1016/j.ccell.2017.04.012 |
Pubmed ID | |
Authors |
Michail S. Lionakis, Kieron Dunleavy, Mark Roschewski, Brigitte C. Widemann, John A. Butman, Roland Schmitz, Yandan Yang, Diane E. Cole, Christopher Melani, Christine S. Higham, Jigar V. Desai, Michele Ceribelli, Lu Chen, Craig J. Thomas, Richard F. Little, Juan Gea-Banacloche, Sucharita Bhaumik, Maryalice Stetler-Stevenson, Stefania Pittaluga, Elaine S. Jaffe, John Heiss, Nicole Lucas, Seth M. Steinberg, Louis M. Staudt, Wyndham H. Wilson |
Abstract |
Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88. We performed a proof-of-concept phase Ib study of ibrutinib monotherapy followed by ibrutinib plus chemotherapy (DA-TEDDi-R). In 18 PCNSL patients, 94% showed tumor reductions with ibrutinib alone, including patients having PCNSL with CD79B and/or MYD88 mutations, and 86% of evaluable patients achieved complete remission with DA-TEDDi-R. Increased aspergillosis was observed with ibrutinib monotherapy and DA-TEDDi-R. Aspergillosis was linked to BTK-dependent fungal immunity in a murine model. PCNSL is highly dependent on BCR signaling, and ibrutinib appears to enhance the efficacy of chemotherapy. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 28 | 39% |
United Kingdom | 6 | 8% |
Australia | 4 | 6% |
France | 3 | 4% |
Germany | 2 | 3% |
Mexico | 2 | 3% |
Spain | 2 | 3% |
Argentina | 1 | 1% |
Portugal | 1 | 1% |
Other | 4 | 6% |
Unknown | 19 | 26% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 39 | 54% |
Scientists | 24 | 33% |
Practitioners (doctors, other healthcare professionals) | 7 | 10% |
Science communicators (journalists, bloggers, editors) | 2 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
Unknown | 223 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 39 | 17% |
Other | 28 | 13% |
Student > Bachelor | 17 | 8% |
Student > Ph. D. Student | 16 | 7% |
Professor | 14 | 6% |
Other | 52 | 23% |
Unknown | 58 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 94 | 42% |
Biochemistry, Genetics and Molecular Biology | 18 | 8% |
Immunology and Microbiology | 15 | 7% |
Agricultural and Biological Sciences | 8 | 4% |
Neuroscience | 5 | 2% |
Other | 19 | 8% |
Unknown | 65 | 29% |