Dataset Information

Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma.

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.

SUBMITTER: Lionakis MS

PROVIDER: S-EPMC5571650 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma.

Lionakis Michail S MS Dunleavy Kieron K Roschewski Mark M Widemann Brigitte C BC Butman John A JA Schmitz Roland R Yang Yandan Y Cole Diane E DE Melani Christopher C Higham Christine S CS Desai Jigar V JV Ceribelli Michele M Chen Lu L Thomas Craig J CJ Little Richard F RF Gea-Banacloche Juan J Bhaumik Sucharita S Stetler-Stevenson Maryalice M Pittaluga Stefania S Jaffe Elaine S ES Heiss John J Lucas Nicole N Steinberg Seth M SM Staudt Louis M LM Wilson Wyndham H WH

Cancer cell 20170525 6

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 w ...[more]

PMID: 28552327

Dataset Information

Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma.

Publications

Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma.

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