Evidence map›Paper›PMID 28924018›Full record

ArticleBlood2017

Ibrutinib for chronic graft-versus-host disease after failure of prior therapy.

David Miklos, Corey S Cutler, Mukta Arora, Edmund K Waller, Madan Jagasia, Iskra Pusic, Mary E Flowers, Aaron C Logan, Ryotaro Nakamura, Bruce R Blazar and 7 more

3 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IMulticenter Study
In one paragraph

Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 274 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
274citing papers in PubMed, 7 pooled it
21.6field-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.

NCT02195869 phase1 / phase2completednot on this map

A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease

TypeinterventionalSponsorPharmacyclics LLC.Ran2014 to 2017Enrolled45ConditionsGraft Versus Host DiseaseArmsIbrutinib
NCT03689894 phase1 / phase2terminatednot on this mapstarted 2019, after this paper: background citation

Combination Ibrutinib and Rituximab for the Treatment of Chronic Graft-Versus-Host Disease Following Allogeneic Stem Cell Transplant

TypeinterventionalSponsorDartmouth-Hitchcock Medical CenterRan2019 to 2021Enrolled2ConditionsChronic Graft-versus-host-diseaseArmsIbrutinib, Rituximab
NCT07576699 phase1 / phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

CK0802 for Treatment of Steroid Refractory Graft vs. Host Disease (GVHD)

TypeinterventionalSponsorCellenkos, Inc.Ran2026 to 2029Enrolled12ConditionsSteroid Refractory Graft Versus Host DiseaseArmsCK0802 (Allogeneic, Cryopreserved, Cord blood-derived T-regulatory cells, cells that are not HLA matched)
3 · Its place in the literature

Who cites it

274 citing papers in PubMed, 7 syntheses or guidelines pooled it, 488 citations in OpenAlex.

  1. Pooled it
  2. Guideline
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  4. Guideline
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Trial
  9. Trial
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  11. A Multicenter Phase II Trial of Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
    Trial
  12. Trial
  13. Trial
  14. Trial
  15. Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023
    Trial
  16. Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023
    Trial
  17. Trial
  18. ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Trial
  19. Trial
  20. Trial

214 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 12 institutions in 1 country.

David MiklosStanford University School of Medicine, Stanford, CA.
Corey S CutlerDana-Farber Cancer Institute, Boston, MA.
Mukta AroraDepartment of Medicine, University of Minnesota, Minneapolis, MN.
Edmund K WallerWinship Cancer Institute of Emory University, Atlanta, GA.
Madan JagasiaVanderbilt-Ingram Cancer Center, Nashville, TN.
Iskra PusicDivision of Oncology, Washington University School of Medicine, St. Louis, MO.
Mary E FlowersFred Hutchinson Cancer Research Center, Seattle, WA.
Aaron C LoganUniversity of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Ryotaro NakamuraCity of Hope, Duarte, CA.
Bruce R BlazarDepartment of Medicine, University of Minnesota, Minneapolis, MN.
Yunfeng LiPharmacyclics LLC, an AbbVie Company, Sunnyvale, CA; and.
Stephen ChangPharmacyclics LLC, an AbbVie Company, Sunnyvale, CA; and.
Indu LalPharmacyclics LLC, an AbbVie Company, Sunnyvale, CA; and.
Jason DubovskyPharmacyclics LLC, an AbbVie Company, Sunnyvale, CA; and.
Danelle F JamesPharmacyclics LLC, an AbbVie Company, Sunnyvale, CA; and.
Lori StylesPharmacyclics LLC, an AbbVie Company, Sunnyvale, CA; and.
Samantha JaglowskiDivision of Hematology, The Ohio State University Cancer Center, Columbus, OH.
AbbVie (United States) · USPharmacyclics (United States) · USUniversity of Minnesota · USCity of Hope · USDana-Farber Cancer Institute · USEmory University · USFred Hutch Cancer Center · USStanford University · USThe Ohio State University · USUCSF Helen Diller Family Comprehensive Cancer Center · USVanderbilt-Ingram Cancer CenterWashington University in St. Louis · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BLAZAR, BRUCE R · 2003 to 2023
$42.5M
Project 3: Humoral Targets and B Cell Biology in Chronic Graft-vs.-Host DiseaseP01CA142106 · NCI · DANA-FARBER CANCER INST · PI RITZ, JEROME · 2009 to 2019
$17.5M
NCI NIH HHS P01 CA142106NCI NIH HHS P30 CA016058NIAID NIH HHS P01 AI056299
6 · The paper itself

Abstract

Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic stem cell transplantation with few effective options available after failure of corticosteroids. B and T cells play a role in the pathophysiology of cGVHD. Ibrutinib inhibits Bruton tyrosine kinase in B cells and interleukin-2-inducible T-cell kinase in T cells. In preclinical models, ibrutinib reduced severity of cGVHD. This multicenter, open-label study evaluated the safety and efficacy of ibrutinib in patients with active cGVHD with inadequate response to corticosteroid-containing therapies. Forty-two patients who had failed 1 to 3 prior treatments received ibrutinib (420 mg) daily until cGVHD progression. The primary efficacy end point was cGVHD response based on 2005 National Institutes of Health criteria. At a median follow-up of 13.9 months, best overall response was 67%; 71% of responders showed a sustained response for ≥20 weeks. Responses were observed across involved organs evaluated. Most patients with multiple cGVHD organ involvement had a multiorgan response. Median corticosteroid dose in responders decreased from 0.29 mg/kg per day at baseline to 0.12 mg/kg per day at week 49; 5 responders discontinued corticosteroids. The most common adverse events were fatigue, diarrhea, muscle spasms, nausea, and bruising. Plasma levels of soluble factors associated with inflammation, fibrosis, and cGVHD significantly decreased over time with ibrutinib. Ibrutinib resulted in clinically meaningful responses with acceptable safety in patients with ≥1 prior treatments for cGVHD. Based on these results, ibrutinib was approved in the United States for treatment of adult patients with cGVHD after failure of 1 or more lines of systemic therapy. This trial was registered at www.clinicaltrials.gov as #NCT02195869.

Indexed as

AdenineAdrenal Cortex HormonesAdultAgammaglobulinaemia Tyrosine KinaseAgedBiomarkersChronic DiseaseDemographyDose-Response Relationship, DrugFemaleGraft vs Host DiseaseHumansMaleMiddle AgedPiperidinesProtein-Tyrosine KinasesAdenineAdrenal Cortex HormonesAgammaglobulinaemia Tyrosine KinaseBiomarkersemt protein-tyrosine kinaseibrutinibPiperidinesProtein-Tyrosine KinasesPyrazolesPyrimidines

Identifiers

PMID28924018
PMCPMC6033048
OpenAlexW2754850852

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.