ArticleHemaSphere2021
Ibrutinib Has Time-dependent On- and Off-target Effects on Plasma Biomarkers and Immune Cells in Chronic Lymphocytic Leukemia.
Article in HemaSphere, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings.Frontiers in immunology · 2024Trial
- Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: Mechanistic Considerations Across Relapsing and Progressive Disease.Molecules (Basel, Switzerland) · 2026Review
- T-cell immunomodulation occurs with different time kinetics during acalabrutinib and zanubrutinib therapy in chronic lymphocytic leukaemia.British journal of haematology · 2026Article
- Cardiovascular Safety of Bruton Tyrosine Kinase Inhibitors: From Ibrutinib to Next-Generation Agents.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026Review
- Generational safety profiles of BTK inhibitors: adverse reaction signals and real-world evidence from the FAERS database.Frontiers in medicine · 2026Article
- Review
- Functional proteoform group deconvolution reveals a broader spectrum of ibrutinib off-targets.Nature communications · 2025Article
- Managing novel therapies and concomitant medications in chronic lymphocytic leukemia: key challenges.Frontiers in pharmacology · 2024Review
- Review
- Zanubrutinib: past, present, and future.Blood cancer journal · 2023Review
- Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management.Signal transduction and targeted therapy · 2023Review
- Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect.Experimental hematology & oncology · 2022Review
- Managing the Risk of Infection in Chronic Lymphocytic Leukemia in the Era of New Therapies.Current oncology reports · 2022Review
- Do reduced numbers of plasmacytoid dendritic cells contribute to the aggressive clinical course of COVID-19 in chronic lymphocytic leukaemia?Scandinavian journal of immunology · 2022Review
- Effects of ibrutinib on T-cell immunity in patients with chronic lymphocytic leukemia.Frontiers in immunology · 2022Review
- Long-Term Efficacy and Safety of Ibrutinib in the Treatment of CLL Patients: A Real Life Experience.Journal of clinical medicine · 2021Article
- Structure-Function Relationships of Covalent and Non-Covalent BTK Inhibitors.Frontiers in immunology · 2021Review
- Clinical Trials of the BTK Inhibitors Ibrutinib and Acalabrutinib in Human Diseases Beyond B Cell Malignancies.Frontiers in oncology · 2021Review
- BTK Inhibitors in Chronic Lymphocytic Leukemia: Biological Activity and Immune Effects.Frontiers in immunology · 2021Review
- Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ibrutinib is a covalently binding inhibitor of the B-cell receptor signaling-mediator Bruton's tyrosine kinase (BTK) with great efficacy in chronic lymphocytic leukemia (CLL). Common side effects like atrial fibrillation (AF), bleeding and infections might be caused by ibrutinib's inhibition of other kinases in non-B cells. Five-year follow-up of plasma biomarkers by proximity extension assay and immune cell numbers by flow cytometry during ibrutinib treatment revealed that 86 of the 265 investigated plasma biomarkers significantly changed during treatment, 74 of which decreased. Among the 12 markers that increased, 6 are associated with cardiovascular diseases and therefore potentially involved in ibrutinib-induced AF. Comparison between healthy donors and X-linked agammaglobulinemia (XLA) patients, who have nonfunctional BTK and essentially lack B cells, showed indicative changes in 53 of the 265 biomarkers while none differed significantly. Hence, neither B cells nor BTK-dependent pathways in other cells seem to influence the levels of the studied plasma biomarkers in healthy donors. Regarding immune cells, the absolute number of T cells, including subsets, decreased, paralleling the decreasing tumor burden. T helper 1 (Th1) cell numbers dropped strongly, while Th2 cells remained relatively stable, causing Th2-skewing. Thus, long-term ibrutinib treatment has a profound impact on the plasma proteome and immune cells in patients with CLL.
Identifiers
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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.