ArticleBlood cancer journal2021
Ibrutinib and venetoclax target distinct subpopulations of CLL cells: implication for residual disease eradication.
Article in Blood cancer journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- A phase 2 study of ibrutinib with venetoclax in Japanese patients with untreated CLL and SLL.International journal of hematology · 2026Trial
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- From Time-Limited Therapy to Treatment-Free Observation: The Evolving Role of MRD in CLL Management.European journal of haematology · 2026Review
- Anti-apoptotic BCL-2 family proteins: from regulatory networks to therapeutic targeting.Oncogenesis · 2026Review
- Fixed-duration ibrutinib-venetoclax for first-line treatment of patients with chronic lymphocytic leukemia: the REALITY-WW prospective real-world study cohort.Future oncology (London, England) · 2025Observational
- Optimizing Ibrutinib Posology in Chronic Lymphocytic Leukemia Using a Semi-Mechanistic Pharmacometric Framework.CPT: pharmacometrics & systems pharmacology · 2025Article
- Shelter in place: live CLL cells inside the bone marrow fibroblasts and its implication in residual disease persistence.Blood neoplasia · 2025Article
- Review
- Comprehensive comparison of enzymatic and bisulfite DNA methylation analysis in clinically relevant samples.Clinical epigenetics · 2025Article
- Targeting the undruggable MYC in cancer: the rationale of using XPO1 inhibitors.Molecular biology reports · 2025Review
- Double Strike in Chronic Lymphocytic Leukemia-The Combination of BTK and BCL2 Inhibitors in Actual and Future Clinical Practice.International journal of molecular sciences · 2025Review
- Ibrutinib and venetoclax in combination for chronic lymphocytic leukemia: synergy in practice.Blood neoplasia · 2024Article
- Review
- Richter transformation acquiringEJHaem · 2024Article
- Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents.Cancers · 2024Review
- Absence of BTK, BCL2, and PLCG2 Mutations in Chronic Lymphocytic Leukemia Relapsing after First-Line Treatment with Fixed-Duration Ibrutinib plus Venetoclax.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Leukemic presentation and progressive genomic alterations of MCD/C5 diffuse large B-cell lymphoma (DLBCL).Cold Spring Harbor molecular case studies · 2023Article
- Article
- Assessment of ibrutinib scheduling on leukocyte, lymph node size and blood pressure dynamics in chronic lymphocytic leukemia through pharmacokinetic-pharmacodynamic models.CPT: pharmacometrics & systems pharmacology · 2023Article
- First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era.Cancers · 2023Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
Ibrutinib inhibits Bruton tyrosine kinase while venetoclax is a specific inhibitor of the anti-apoptotic protein BCL2. Both drugs are highly effective as monotherapy against chronic lymphocytic leukemia (CLL), and clinical trials using the combination therapy have produced remarkable results in terms of rate of complete remission and frequency of undetectable minimal residual disease. However, the laboratory rationale behind the success of the drug combination is still lacking. A better understanding of how these two drugs synergize would eventually help develop other rational combination strategies. Using an ex vivo model that promotes CLL proliferation, we show that modeled ibrutinib proliferative responses, but not viability responses, correlate well with patients' actual clinical responses. Importantly, we demonstrate for the first time that ibrutinib and venetoclax act on distinct CLL subpopulations that have different proliferative capacities. While the dividing subpopulation of CLL responds to ibrutinib, the resting subpopulation preferentially responds to venetoclax. The combination of these targeted therapies effectively reduced both the resting and dividing subpopulations in most cases. Our laboratory findings help explain several clinical observations and contribute to the understanding of tumor dynamics. Additionally, our proliferation model may be used to identify novel drug combinations with the potential of eradicating residual disease.
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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.