ArticleBlood2014
Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy.
Article 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 NCT02446236 (Phase Ib Dose Finding Study of Bruton's Tyrosine Kinase), which is not on this map. Cited by 137 papers, 1 of them a synthesis that pooled it.
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.
Phase Ib Dose Finding Study of Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765) Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma (MCL)
Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 273 citations in OpenAlex.
- Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 1.2015.Journal of the National Comprehensive Cancer Network : JNCCN · 2015Guideline
- Acalabrutinib and high-frequency low-dose subcutaneous rituximab for initial therapy of chronic lymphocytic leukemia.Blood advances · 2023Trial
- Trial
- Acalabrutinib plus Obinutuzumab in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia.Cancer discovery · 2020Trial
- Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL.The New England journal of medicine · 2018Trial
- 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
- Ruxolitinib for symptom control in patients with chronic lymphocytic leukaemia: a single-group, phase 2 trial.The Lancet. Haematology · 2017Trial
- Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial.British journal of haematology · 2017Trial
- Trial
- Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial.The Lancet. Oncology · 2015Trial
- Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study.Leukemia · 2014Trial
- Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study.The Lancet. Oncology · 2014Trial
- Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.The New England journal of medicine · 2014Trial
- Trial
- A prospective, multi-center, phase IV clinical study to assess the safety and clinical outcome of acalabrutinib in Indian adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma or relapsed/refractory mantle cell lymphoma.Frontiers in oncology · 2026Article
- Optimizing Ibrutinib Posology in Chronic Lymphocytic Leukemia Using a Semi-Mechanistic Pharmacometric Framework.CPT: pharmacometrics & systems pharmacology · 2025Article
- High lymphocyte count and bleeding risk in patients with chronic lymphocytic leukemia treated with Bruton's tyrosine kinase inhibitors.Wiener klinische Wochenschrift · 2025Article
- Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice.Leukemia · 2025Review
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 5 institutions in 1 country.
Funding
Abstract
The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has outstanding activity in patients with chronic lymphocytic leukemia. Most patients experience lymphocytosis, representing lymphocyte egress from nodal compartments. This resolves within 8 months in the majority of patients, but a subgroup has lymphocytosis lasting >12 months. Here we report a detailed characterization of patients with persistent lymphocytosis during ibrutinib therapy. Signaling evaluation showed that while BTK is inhibited, downstream mediators of B-cell receptor (BCR) signaling are activated in persistent lymphocytes. These cells cannot be stimulated through the BCR and do not show evidence of target gene activation. Flow cytometry for κ and λ expression, IGHV sequencing, Zap-70 methylation, and targeted gene sequencing in these patients are identical at baseline and later time points, suggesting that persistent lymphocytes do not represent clonal evolution. In vitro treatment with targeted kinase inhibitors shows that they are not addicted to a single survival pathway. Finally, progression-free survival is not inferior for patients with prolonged lymphocytosis vs those with traditional responses. Thus, prolonged lymphocytosis is common following ibrutinib treatment, likely represents the persistence of a quiescent clone, and does not predict a subgroup of patients likely to relapse early.
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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.