ArticleCancer cell2017
Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Cancer cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04066920 (Clinical Efficacy and Safety of IBER Salvage Treatment Followed by Ibrutinib Maintenance for Transplant-ineligible Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma), which is not on this map. Cited by 265 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
265citing papers in PubMed, 3 pooled it
35.7field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical Efficacy and Safety of IBER Salvage Treatment Followed by Ibrutinib Maintenance for Transplant-ineligible Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma (PCNSL): a Multicenter, Single-arm, Prospective Phase II Study
Who cites it
265 citing papers in PubMed, 3 syntheses or guidelines pooled it, 490 citations in OpenAlex.
- Invasive fungal infections after Bruton tyrosine kinase inhibitor treatment: a systematic review and meta-analysis.Blood advances · 2026Pooled it
- Aspergillus fumigatus-a systematic review to inform the World Health Organization priority list of fungal pathogens.Medical mycology · 2024Pooled it
- Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis.Frontiers in oncology · 2021Pooled it
- A multicenter randomized phase II/III trial of salvage treatment for refractory primary central nervous system lymphoma using tirabrutinib: JCOG2314 (ReSTART).Japanese journal of clinical oncology · 2026Trial
- Zanubrutinib combined with R-CHOP in previously untreated diffuse large B-cell lymphoma with specific gene alteration: a phase II study.Blood cancer journal · 2026Trial
- High-Dose Methotrexate, Ibrutinib, and Temozolomide in the Treatment of Newly Diagnosed Primary CNS Lymphoma: A Multicenter, Prospective Phase II Study.Blood cancer discovery · 2025Trial
- Prospective phase II trial of first-line rituximab, methotrexate, and orelabrutinib (R-MO) in primary central nervous system lymphoma.Blood cancer journal · 2025Trial
- Phase 2 trial of ibrutinib and nivolumab in patients with relapsed CNS lymphomas.Blood advances · 2025Trial
- Phase II Trial of an Orelabrutinib-Based Combination Therapy in Newly Diagnosed Primary Central Nervous System Lymphoma.Blood and lymphatic cancer : targets and therapy · 2025Trial
- Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients.Journal of hematology & oncology · 2024Trial
- A Phase II Study Assessing Long-term Response to Ibrutinib Monotherapy in Recurrent or Refractory CNS Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma.The New England journal of medicine · 2024Trial
- Improving the antitumor activity of R-CHOP with NGR-hTNF in primary CNS lymphoma: final results of a phase 2 trial.Blood advances · 2020Trial
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Advances in molecular pathobiology of PCNSL - towards clinical implementation of novel diagnostics and therapeutics.Biomarker research · 2026Review
- Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma.American journal of hematology · 2026Article
- Primary central nervous system lymphoma in the molecular era: genomic drivers, liquid biopsy, and targeted therapeutic strategies.Annals of hematology · 2026Review
- Dural Lymphomas Unmasked: A Narrative Review of Extra-Axial Mimics and a Pragmatic Diagnostic Decision Algorithm.Cancers · 2026Review
- Clinical Impact of BTK Inhibitor Exposure in LymphGen-Defined MCD Diffuse Large B-Cell Lymphoma.Hematological oncology · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
205 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
25 authors at 2 institutions in 1 country.
Michail S LionakisLaboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kieron DunleavyLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mark RoschewskiLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Brigitte C WidemannPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
John A ButmanRadiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Roland SchmitzLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yandan YangLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Diane E ColePediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Christopher MelaniLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Christine S HighamPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jigar V DesaiLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Michele CeribelliDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA.
Lu ChenDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA.
Craig J ThomasLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Gaithersburg, MD 20850, USA.
Richard F LittleCancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Juan Gea-BanaclochePediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sucharita BhaumikPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Maryalice Stetler-StevensonPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Stefania PittalugaPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Elaine S JaffePediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
John HeissPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nicole LucasLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Seth M SteinbergPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Louis M StaudtLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lstaudt@mail.nih.gov.
Wyndham H WilsonLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: wilsonw@mail.nih.gov.
National Institutes of Health · USNational Institutes of Health Clinical Center · US
Funding
Immunopathogenesis of Fungal InfectionsZIAAI001175 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LIONAKIS, MICHAIL · 2012 to 2025
$23.9MMolecular Pathogenesis of NeoplasiaZIANS003052 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI HEISS, JOHN · 2009 to 2025
$20.7MHematopathology DiagnosisZIABC011070 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI JAFFE, ELAINE · 2009 to 2025
$14.5MTherapeutic Strategies and Molecular Correlates in Aggressive B-cell LymphomasZIASC006741 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI WILSON, WYNDHAM H · 2009 to 2025
$10.4MHTS enabled examination of drug combinationsZIATR000047 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI THOMAS, CRAIG · 2015 to 2025
$7.1MTargeted treatment of B-cell LymphomaZIABC011354 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WILSON, WYNDHAM H · 2010 to 2025
$4.6MFLow Cytometric Detection of Malignant Cells in Body FluidsZICBC011093 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, HAO-WEI · 2009 to 2025
$4.5MTEDDI-R in PCNSLZIABC011654 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WILSON, WYNDHAM H · 2015 to 2021
$1.5MLYMPHOMA STUDIESZ01SC006741 · SC · DIVISION OF CLINICAL SCIENCES - NCI · PI WILSON, WYNDHAM H · 1996 to 2008
$893kIntramural NIH HHS Z01 SC006741Intramural NIH HHS ZIA BC011354Intramural NIH HHS ZIA BC011654
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.
Indexed as
AdenineAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overAnimalsAspergillosisBrain NeoplasmsCD79 AntigensDrug Therapy, CombinationEnzyme InhibitorsFemaleGene Knockout TechniquesHumansLymphomaMaleMiceAdenineAgammaglobulinaemia Tyrosine KinaseBTK protein, humanBtk protein, mouseCD79 AntigensEnzyme InhibitorsibrutinibMYD88 protein, humanMyeloid Differentiation Factor 88PiperidinesProtein-Tyrosine KinasesPyrazolesPyrimidinesReceptors, Antigen, B-CellABC DLBCLAspergillus fumigatusB cell receptor signalingBTKibrutinibmacrophageprimary CNS lymphoma
Identifiers
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Registered trials
NCT04066920ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.