Evidence map›Paper›PMID 26193343›Full record

Trial reportNature medicine2015

Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma.

Wyndham H Wilson, Ryan M Young, Roland Schmitz, Yandan Yang, Stefania Pittaluga, George Wright, Chih-Jian Lih, P Mickey Williams, Arthur L Shaffer, John Gerecitano and 20 more

2 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 596 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
596citing papers in PubMed, 2 pooled it
58.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

NCT03136497 phase1terminatednot on this mapstarted 2017, after this paper: background citation

Phase Ib Dose Finding Study of ABT-199 (A-1195425.0) Plus Ibrutinib (PCI-32765) and Rituximab in Patients With Relapsed/Refractory Diffuse Large B-cell NHL (DLBCL)

TypeinterventionalSponsorHackensack Meridian HealthRan2017 to 2020Enrolled10ConditionsRelapsed Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell LymphomaArms400mg ABT-199, Ibrutinib, Rituximab, 800mg ABT-199
NCT04066920 phase2unknown statusnot on this mapstarted 2019, after this paper: background citation

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

TypeinterventionalSponsorDeok-Hwan YangRan2019 to 2023Enrolled30ConditionsPrimary Central Nervous System LymphomaArmsIBER salvage chemotherapy followed by ibrutinib maintenance therapy
3 · Its place in the literature

Who cites it

596 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,102 citations in OpenAlex.

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  8. 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 · 2024
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536 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors at 16 institutions in 1 country.

Wyndham H WilsonLymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.
Ryan M YoungLymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.
Roland SchmitzLymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.
Yandan YangLymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.
Stefania PittalugaLaboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland, USA.
George WrightBiometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Chih-Jian LihFrederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
P Mickey WilliamsFrederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Arthur L ShafferLymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.
John Gerecitano1] Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2] Department of Medicine, Weill Cornell Medical College, New York, New York, USA.
Sven de VosDivision of Hematology and Oncology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.
Andre GoyJohn Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey, USA.
Vaishalee P KenkreDivision of Hematology and Medical Oncology, University of Wisconsin, Madison, Wisconsin, USA.
Paul M BarrJames P. Wilmot Cancer Center, University of Rochester, Rochester, New York, USA.
Kristie A BlumDivision of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Andrei ShustovDepartment of Medicine, Hematology, University of Washington School of Medicine, Seattle, Washington, USA.
Ranjana AdvaniMedical Oncology, Stanford University Medical Center, Stanford, California, USA.
Nathan H FowlerDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Julie M VoseDivision of Hematology &Oncology, Department of Internal Medicine, University of Nebraska, Omaha, Nebraska, USA.
Rebecca L ElstromClinical Development, Genentech, Inc., South San Francisco, California, USA.
Thomas M HabermannDivision of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Jacqueline C BarrientosDivision of Hematology and Medical Oncology, Department of Medicine, Hofstra North Shore-Long Island Jewish School of Medicine, Hempstead, New York, USA.ORCID 0000000160185535
Jesse McGreivyPharmacyclics, Inc., Sunnyvale, California, USA.
Maria FardisPharmacyclics, Inc., Sunnyvale, California, USA.
Betty Y ChangPharmacyclics, Inc., Sunnyvale, California, USA.
Fong ClowPharmacyclics, Inc., Sunnyvale, California, USA.
Brian MunnekePharmacyclics, Inc., Sunnyvale, California, USA.
Davina MoussaPharmacyclics, Inc., Sunnyvale, California, USA.
Darrin M BeauprePharmacyclics, Inc., Sunnyvale, California, USA.
Louis M StaudtLymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA.
National Institutes of Health · USPharmacyclics (United States) · USFrederick National Laboratory for Cancer Research · USAcentech (United States) · USHofstra University · USMayo Clinic · USMemorial Sloan Kettering Cancer Center · USRutgers, The State University of New Jersey · USStanford Medicine · USThe Ohio State University · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, Los Angeles · USUniversity of Nebraska at Omaha · USUniversity of Rochester · USUniversity of Washington · USUniversity of Wisconsin–Madison · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Therapeutic Strategies and Molecular Correlates in Aggressive B-cell LymphomasZIASC006741 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI WILSON, WYNDHAM H · 2009 to 2025
$10.4M
Molecular diagnosis and outcome prediction in lymphomaZ01BC011006 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI STAUDT, LOUIS · 2008 to 2008
$770k
Intramural NIH HHS Z01 BC011006Intramural NIH HHS ZIA SC006741
6 · The paper itself

Abstract

The two major subtypes of diffuse large B cell lymphoma (DLBCL)--activated B cell-like (ABC) and germinal center B cell-like (GCB)--arise by distinct mechanisms, with ABC selectively acquiring mutations that target the B cell receptor (BCR), fostering chronic active BCR signaling. The ABC subtype has a ∼40% cure rate with currently available therapies, which is worse than the rate for GCB DLBCL, and highlights the need for ABC subtype-specific treatment strategies. We hypothesized that ABC, but not GCB, DLBCL tumors would respond to ibrutinib, an inhibitor of BCR signaling. In a phase 1/2 clinical trial that involved 80 subjects with relapsed or refractory DLBCL, ibrutinib produced complete or partial responses in 37% (14/38) of those with ABC DLBCL, but in only 5% (1/20) of subjects with GCB DLBCL (P = 0.0106). ABC tumors with BCR mutations responded to ibrutinib frequently (5/9; 55.5%), especially those with concomitant myeloid differentiation primary response 88 (MYD88) mutations (4/5; 80%), a result that is consistent with in vitro cooperation between the BCR and MYD88 pathways. However, the highest number of responses occurred in ABC tumors that lacked BCR mutations (9/29; 31%), suggesting that oncogenic BCR signaling in ABC does not require BCR mutations and might be initiated by non-genetic mechanisms. These results support the selective development of ibrutinib for the treatment of ABC DLBCL.

Indexed as

AdenineAdultAgedBase SequenceCD79 AntigensFemaleHumansLymphoma, Large B-Cell, DiffuseMaleMiddle AgedMolecular Sequence DataMutationMyeloid Differentiation Factor 88PiperidinesProtein Kinase InhibitorsPyrazolesAdenineCD79 AntigensCD79A protein, humanibrutinibMYD88 protein, humanMyeloid Differentiation Factor 88PiperidinesProtein Kinase InhibitorsPyrazolesPyrimidinesReceptors, Antigen, B-Cell

Identifiers

PMID26193343
PMCPMC8372245
OpenAlexW1020989877

What OpenQuestion holds

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Registered trials

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.