| Literature DB >> 28552327 |
Michail S Lionakis1, Kieron Dunleavy2, Mark Roschewski2, Brigitte C Widemann3, John A Butman4, Roland Schmitz2, Yandan Yang2, Diane E Cole3, Christopher Melani2, Christine S Higham3, Jigar V Desai2, Michele Ceribelli5, Lu Chen5, Craig J Thomas6, Richard F Little7, Juan Gea-Banacloche3, Sucharita Bhaumik3, Maryalice Stetler-Stevenson3, Stefania Pittaluga3, Elaine S Jaffe3, John Heiss3, Nicole Lucas2, Seth M Steinberg3, Louis M Staudt8, Wyndham H Wilson9.
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. Published by Elsevier Inc.Entities:
Keywords: ABC DLBCL; Aspergillus fumigatus; B cell receptor signaling; BTK; ibrutinib; macrophage; primary CNS lymphoma
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Year: 2017 PMID： 28552327 PMCID： PMC5571650 DOI： 10.1016/j.ccell.2017.04.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743