ArticleCancer discovery2017
Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.
Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase I
In one paragraph
Article in Cancer discovery, 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 211 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
211citing papers in PubMed, 3 pooled it
23.4field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
211 citing papers in PubMed, 3 syntheses or guidelines pooled it, 394 citations in OpenAlex.
- Efficacy and Safety of Axicabtagene Ciloleucel and Tisagenlecleucel Administration in Lymphoma Patients With Secondary CNS Involvement: A Systematic Review.Frontiers in immunology · 2021Pooled it
- Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Primary Pituitary Lymphoma in Immunocompetent Patients: A Report on Two Case Studies and the Review of Literature.Frontiers in endocrinology · 2020Pooled 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
- Penpulimab combined with rituximab, high-dose methotrexate, and cytarabine (Pen-RMA) in newly diagnosed primary central nervous system lymphoma (PCNSL): a phase 2 trial.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
- Trial
- 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
- Trial
- A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial.Blood advances · 2021Trial
- A single-center retrospective analysis of outcome measures and consolidation strategies for relapsed and refractory primary CNS lymphoma.Journal of neuro-oncology · 2021Trial
- Improving the antitumor activity of R-CHOP with NGR-hTNF in primary CNS lymphoma: final results of a phase 2 trial.Blood advances · 2020Trial
- Advances in molecular pathobiology of PCNSL - towards clinical implementation of novel diagnostics and therapeutics.Biomarker research · 2026Review
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Primary central nervous system lymphoma in the molecular era: genomic drivers, liquid biopsy, and targeted therapeutic strategies.Annals of hematology · 2026Review
- Clinical Impact of BTK Inhibitor Exposure in LymphGen-Defined MCD Diffuse Large B-Cell Lymphoma.Hematological oncology · 2026Article
151 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
42 authors at 1 institution in 1 country.
Christian GrommesDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
Alessandro PastoreDepartment of Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Nicolaos PalaskasHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Sarah S TangHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Carl CamposHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Derrek SchartzHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Paolo CodegaHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Donna NicholHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Owen ClarkHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Wan-Ying HsiehHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Dan RohleHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Marc RosenblumDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Agnes VialeMarie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Viviane S TabarDepartment of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Cameron W BrennanDepartment of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Igor T GavrilovicDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
Thomas J KaleyDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
Craig P NolanDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
Antonio OmuroDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
Elena PentsovaDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
Alissa A ThomasDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
Elina TsyvkinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Ariela NoyDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
M Lia PalombaDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Paul HamlinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Craig S SauterDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Craig H MoskowitzDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Julia WolfeDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
Ahmet DoganDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Minhee WonNRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
Jon GlassDepartment of Neurosurgery, Thomas Jefferson University, Philadelphia, Pennsylvania.
Scott PeakDepartment of Neurosurgery, The Permanente Medical Group, Sacramento, California.
Enrico C LallanaDepartment of Neuro-Oncology, The Permanente Medical Group, Redwood City, California.
Vaios HatzoglouDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
Anne S ReinerDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Philip H GutinDepartment of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Jason T HuseHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Katherine S PanageasDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Thomas G GraeberDepartment of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California, Los Angeles, California.
Nikolaus SchultzHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. mellingi@mskcc.org deangell@mskcc.org schultz@cbio.mskcc.org.
Lisa M DeAngelisDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York. mellingi@mskcc.org deangell@mskcc.org schultz@cbio.mskcc.org.
Ingo K MellinghoffDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York. mellingi@mskcc.org deangell@mskcc.org schultz@cbio.mskcc.org.
Memorial Sloan Kettering Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MNRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8MTranslating Stress Response Targeted Therapy for B-Cell LymphomasP50CA192937 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ZELENETZ, ANDREW D. · 2016 to 2020
$10.9MMolecular Mechanisms of Drug Resistance in Primary Brain TumorsR35NS105109 · NINDS · SLOAN-KETTERING INST CAN RESEARCH · PI MELLINGHOFF, INGO K · 2018 to 2025
$4.7MMolecular Mechanisms of IDH1-mediated GliomagenesisR01NS080944 · NINDS · SLOAN-KETTERING INST CAN RESEARCH · PI MELLINGHOFF, INGO K · 2012 to 2016
$2.0MInvestigating Bruton's Tyrosine Kinase Dependency in Primary Central Nervous System LymphomaF31CA220985 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI TANG, SARAH · 2017 to 2020
$179kNCI NIH HHS F31 CA220985NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA192937NCI NIH HHS U10 CA180868NINDS NIH HHS R01 NS080944NINDS NIH HHS R35 NS105109
Abstract
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.
Indexed as
AdenineAdultAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overAntineoplastic AgentsCARD Signaling Adaptor ProteinsCentral Nervous System NeoplasmsDrug Resistance, NeoplasmFemaleGuanylate CyclaseHumansLymphoma, B-CellMaleMaximum Tolerated DoseMiddle AgedAdenineAgammaglobulinaemia Tyrosine KinaseAntineoplastic AgentsBTK protein, humanCARD11 protein, humanCARD Signaling Adaptor ProteinsGuanylate CyclaseibrutinibPiperidinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyrimidines
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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.