Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy
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Key Points: Persistent CLL cells during ibrutinib therapy show evidence of biochemical activation, but inhibited BCR and no proliferation. Long lymphocytosis during ibrutinib therapy is not associated with adverse progression-free survival.
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In patients treated with ibrutinib, a characteristic lymphocytosis develops as CLL cells are mobilized from lymph nodes and the spleen.
“In patients treated with ibrutinib, a characteristic lymphocytosis develops as CLL cells are mobilized from lymph nodes and the spleen.”
From Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib (2014) · cites this paper as [24]
The Results report that lymphocytosis occurred in 77% of patients treated with ibrutinib, and the Introduction describes cell mobilization from nodal and marrow sites as a possible mechanism. Our copy does not identify the spleen as a source of the mobilized CLL cells, so that part of the claim is unsupported. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAlthough lymphocytosis typically resolves within 8 months, a subgroup of patients have lymphocytosis that lasts longer than 12 months in the presence of a continued response to ibrutinib.
“Although lymphocytosis typically resolves within 8 months, a subgroup of patients have lymphocytosis that lasts longer than 12 months in the presence of a continued response to ibrutinib.24”
From Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib (2014) · cites this paper as [24]
BTK and PLCγ2 are inhibited in patients with persistent lymphocytosis during ibrutinib treatment.
“We have previously documented by immunoblot analysis24 that BTK and PLCγ2 are inhibited in these patients”
From Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib (2014) · cites this paper as [24]
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Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib
Woyach, J. A., Furman, R. R., Liu, T.-M., Ozer, H. G., Zapatka, M., Ruppert, A. S., Xue, L., Li, D. H.-H., Steggerda, S. M., Versele, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400029 · Cited by 1,275 · see citing works
Self-citationEvolution of ibrutinib resistance in chronic lymphocytic leukemia (CLL)
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- Authors
- Woyach, J. A., Smucker, K., Smith, L. L., Lozanski, A., Zhong, Y., Ruppert, A. S., Lucas, D., Williams, K., Zhao, W., Rassenti, L., Ghia, E., Kipps, T. J., Mantel, R., Jones, J., Flynn, J., Maddocks, K., O’Brien, S., Furman, R. R., James, D. F., Clow, F., Lozanski, G., Johnson, A. J., & Byrd, J. C.
- Affiliations
- Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and
- The Ohio State University (US)
- CLL Research Consortium, La Jolla, CA;
- University of California San Diego (US)
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;
- Weill Cornell Medicine (US)
- Pharmacyclics (United States) (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2014-03-20
- Volume
- 123
- Issue
- 12
- Pages
- 1810-1817
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3962160
- OpenAlex
- W2157799317
- Cited by
- 280
- References
- 0
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 12 · 2023: 6 · 2022: 8 · 2021: 15 · 2020: 24 · 2019: 22 · 2018: 22 · 2017: 45 · 2016: 38 · 2015: 39 · 2014: 35 · 2012: 1
- FWCI
- 26.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (4p01ca081534-16)
- National Cancer Institute (P50CA140158, R01CA183444, K23CA178183, P30CA016672, P30CA016058, K12CA133250, R01CA177292, P01-CA-081534)
- Topics
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- ibrutinib, chronic lymphocytic leukemia, BTK inhibitors, B cell receptor signaling, clonal evolution, progression-free survival, recurrence prediction, IGHV gene usage
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Adenine, Adult, Aged, Aged, 80 and over, Female, Humans, Lymphocytes, Lymphocytosis, Male, Middle Aged, Phosphorylation, Piperidines, Prognosis, Protein-Tyrosine Kinases, Pyrazoles, Pyrimidines, Receptors, Antigen, B-Cell, Signal Transduction, Leukemia, Lymphocytic, Chronic, B-Cell, Disease-Free Survival, CD40 Ligand, Protein Kinase Inhibitors, ZAP-70 Protein-Tyrosine Kinase, Phospholipase C gamma
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