The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma
Open accessAbstract
BACKGROUND: Bruton's tyrosine kinase (BTK) is a mediator of the B-cell-receptor signaling pathway implicated in the pathogenesis of B-cell cancers. In a phase 1 study, ibrutinib, a BTK inhibitor, showed antitumor activity in several types of non-Hodgkin's lymphoma, including mantle-cell lymphoma. METHODS: In this phase 2 study, we investigated oral ibrutinib, at a daily dose of 560 mg, in 111 patients with relapsed or refractory mantle-cell lymphoma. Patients were enrolled into two groups: those who had previously received at least 2 cycles of bortezomib therapy and those who had received less than 2 complete cycles of bortezomib or had received no prior bortezomib therapy. The primary end point was the overall response rate. Secondary end points were duration of response, progression-free survival, overall survival, and safety. RESULTS: The median age was 68 years, and 86% of patients had intermediate-risk or high-risk mantle-cell lymphoma according to clinical prognostic factors. Patients had received a median of three prior therapies. The most common treatment-related adverse events were mild or moderate diarrhea, fatigue, and nausea. Grade 3 or higher hematologic events were infrequent and included neutropenia (in 16% of patients), thrombocytopenia (in 11%), and anemia (in 10%). A response rate of 68% (75 patients) was observed, with a complete response rate of 21% and a partial response rate of 47%; prior treatment with bortezomib had no effect on the response rate. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months (95% confidence interval [CI], 15.8 to not reached), the estimated median progression-free survival was 13.9 months (95% CI, 7.0 to not reached), and the median overall survival was not reached. The estimated rate of overall survival was 58% at 18 months. CONCLUSIONS: Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01236391.)
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“However, it is not selective for BTK, and multiple mechanisms of resistance, including the C481S-BTK mutation, can compromise its efficacy.”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [8]
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“often due to the C481S mutation of BTK, which prevents ibrutinib from forming a covalent bond with BTK and significantly reduces its potency, resulting in median progression-free survival of only ;14 months.8”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [8]
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“often due to the C481S mutation of BTK, which prevents ibrutinib from forming a covalent bond with BTK and significantly reduces its potency, resulting in median progression-free survival of only ;14 months.8”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [8]
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Self-citationChronic active B-cell-receptor signalling in diffuse large B-cell lymphoma
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Self-citationSmall molecules in targeted cancer therapy: advances, challenges, and future perspectives
Zhong, L., Li, Y., Xiong, L., Wang, W., Wu, M., Yuan, T., Yang, W. M., Tian, C., Miao, Z., Wang, T., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00572-w · Cited by 1,813
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Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma
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Metadata
- Authors
- Wang, M. L., Rule, S., Martin, P., Goy, A., Auer, R., Kahl, B. S., Jurczak, W., Advani, R. H., Romaguera, J. E., Williams, M. E., Barrientos, J. C., Chmielowska, E., Radford, J., Stilgenbauer, S., Dreyling, M., Jedrzejczak, W. W., Johnson, P., Spurgeon, S. E., Li, L., Zhang, L., Newberry, K., Ou, Z., Cheng, N., Fang, B., McGreivy, J., Clow, F., Buggy, J. J., Chang, B. Y., Beaupre, D. M., Kunkel, L. A., & Blum, K. A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Derriford Hospital (GB)
- Weill Cornell Medicine (US)
- Hackensack University Medical Center (US)
- University of Wisconsin–Madison (US)
- Jagiellonian University (PL)
- Stanford Medicine (US)
- University of Virginia (US)
- Northwell Health (US)
- Centrum Onkologii (PL)
- University of Manchester (GB)
- University Hospital Ulm (DE)
- LMU Klinikum (DE)
- Cancer Research UK (GB)
- Oregon Health & Science University (US)
- Pharmacyclics (United States) (US)
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- ORCID
- Wang, Michael L.
- Rule, Simon
- Martin, Peter
- Goy, Andre
- Auer, Rebecca
- Kahl, Brad S.
- Jurczak, Wojciech
- Advani, Ranjana H.
- Romaguera, Jorge E.
- Williams, Michael E.
- Barrientos, Jacqueline C.
- Radford, John
- Stilgenbauer, Stephan
- Dreyling, Martin
- Johnson, Peter
- Spurgeon, Stephen E.
- Li, Lei
- Zhang, Liang
- Newberry, Kate
- Fang, Bingliang
- Chang, Betty Y.
- Blum, Kristie A.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2013-08-08
- Volume
- 369
- Issue
- 6
- Pages
- 507-516
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4513941
- OpenAlex
- W2154066874
- Cited by
- 1,685
- References
- 39
- Citations by year
- 2026: 59 · 2025: 67 · 2024: 91 · 2023: 115 · 2022: 142 · 2021: 127 · 2020: 138 · 2019: 127 · 2018: 141 · 2017: 161 · 2016: 133 · 2015: 189 · 2014: 147 · 2013: 42
- FWCI
- 127.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
- Funders
- American Society of Hematology
- Amgen
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Gilead Sciences
- Celgene
- Massachusetts Medical Society
- Les Laboratories Pierre Fabre
- Genentech
- Pharmacyclics
- National Cancer Institute (P30CA014520)
- Janssen Biotech
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Clinical Neurology › CNS Lymphoma Diagnosis and Treatment
- Keywords
- ibrutinib, BTK inhibitors, mantle cell lymphoma, relapsed/refractory lymphoma, bortezomib, B cell receptor signaling, oral BTK inhibitor, overall response rate, progression-free survival, overall survival, adverse events, neutropenia
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Adenine, Administration, Oral, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Piperidines, Protein-Tyrosine Kinases, Pyrazoles, Pyrimidines, Recurrence, Survival Analysis, Lymphocyte Count, Drug Resistance, Neoplasm, Lymphoma, Mantle-Cell, Protein Kinase Inhibitors
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