Trial reportBlood2014
Ibrutinib inhibits BCR and NF-κB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL.
Trial report in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01500733 (A Phase II Study of PCI-32765 for Patients With Chronic Lymphocytic Leukemia), which is not on this map. Cited by 163 papers, 2 of them syntheses that pooled 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.
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.
A Phase II Study of PCI-32765 for Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Need Therapy and Are Older Than 65 or Have a 17p Deletion
Who cites it
163 citing papers in PubMed, 2 syntheses or guidelines pooled it, 241 citations in OpenAlex.
- Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Resistance-Associated Mutations in Chronic Lymphocytic Leukemia Patients Treated With Novel Agents.Frontiers in oncology · 2020Pooled it
- A Phase I/II Study of Ibrutinib Plus Trastuzumab in HER2-Positive Metastatic Breast Cancer.Cancer medicine · 2026Trial
- Trial
- Pharmacodynamic Analysis of BTK Inhibition in Patients with Chronic Lymphocytic Leukemia Treated with Acalabrutinib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Acalabrutinib plus Obinutuzumab in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia.Cancer discovery · 2020Trial
- Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia.The New England journal of medicine · 2019Trial
- Ibrutinib therapy downregulates AID enzyme and proliferative fractions in chronic lymphocytic leukemia.Blood · 2019Trial
- Outcomes with ibrutinib by line of therapy and post-ibrutinib discontinuation in patients with chronic lymphocytic leukemia: Phase 3 analysis.American journal of hematology · 2019Trial
- Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL.The New England journal of medicine · 2018Trial
- A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia.Blood · 2018Trial
- Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study.Blood · 2018Trial
- BTKJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Trial
- Trial
- Extended Treatment with Single-Agent Ibrutinib at the 420 mg Dose Leads to Durable Responses in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Hair and Nail Changes During Long-term Therapy With Ibrutinib for Chronic Lymphocytic Leukemia.JAMA dermatology · 2016Trial
- Disruption of in vivo Chronic Lymphocytic Leukemia Tumor-Microenvironment Interactions by Ibrutinib--Findings from an Investigator-Initiated Phase II Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia.The New England journal of medicine · 2015Trial
- Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.Haematologica · 2015Trial
- Trial
103 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental factors for proliferation and survival. In particular, tissue-resident CLL cells show prominent activation of both B-cell receptor (BCR) and NF-κB pathways. We evaluated the in vivo effects of ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor on tumor cell activation and proliferation in the blood, lymph node, and bone marrow of patients with CLL. Applying validated pathway-specific gene signatures, we detected a rapid and sustained downregulation of BCR and NF-κB signaling in CLL cells from both the peripheral blood and tissue compartments during ibrutinib treatment. Ibrutinib reduced phosphorylation of PLCγ2 and ERK and decreased nuclear protein expression of NF-κB p50. Ibrutinib significantly decreased tumor proliferation and expression of surface activation markers CD69 and CD86, independent of prognostic factors such as IGHV mutational status, chromosome 17p deletion, or prior treatment history. Interestingly, stronger inhibition of BCR signaling in lymph node resident CLL cells after one dose of ibrutinib was associated with a higher rate of nodal response at the end of cycle 2. Together, these data validate on-target effects of BTK inhibition in the tissue compartments and demonstrate that ibrutinib effectively inhibits pathways that promote tumor cell activation and proliferation in vivo. This study is registered at www.clinicaltrials.gov as #NCT01500733.
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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.