ArticleBlood advances2022
Enrichment of BTK Leu528Trp mutations in patients with CLL on zanubrutinib: potential for pirtobrutinib cross-resistance.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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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
55 citing papers in PubMed, 92 citations in OpenAlex.
- Docirbrutinib is a pan-mutant BTK inhibitor and inhibits B-cell receptor signaling in chronic lymphocytic leukemia cells in preclinical and early clinical investigations.Blood cancer journal · 2026Trial
- Trial
- Acquired mutations in patients with relapsed/refractory CLL who progressed in the ALPINE study.Blood advances · 2025Trial
- Trial
- Computational hybrid framework integrating clinical-mutation profiling and physics-based simulations to predict structural tolerance of Bruton tyrosine kinase (BTK) and sustained ARQ 531 binding.Current research in structural biology · 2026Article
- Comparable outcomes of BTK inhibitors and fixed-duration venetoclax plus rituximab in second-line treatment of chronic lymphocytic leukaemia: a real-world analysis by the Czech CLL study group.Annals of hematology · 2026Article
- When Targeted Therapy Falls Short: Unraveling Resistance Mechanisms in Chronic Lymphocytic Leukemia.Current hematologic malignancy reports · 2026Review
- Zanubrutinib in B-cell lymphomas: from clinical pharmacology to therapeutic application.European journal of clinical pharmacology · 2026Review
- Pirtobrutinib in the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma.Future oncology (London, England) · 2025Review
- Management of Relapsed and/or Refractory Chronic Lymphocytic Leukemia.Hematology/oncology clinics of North America · 2025Review
- Review
- Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice.Leukemia · 2025Review
- Resistance mechanisms and approach to chronic lymphocytic leukemia after BTK inhibitor therapy.Leukemia & lymphoma · 2025Review
- Multiplex digital PCR enables sensitive detection of resistance to BTK inhibitors.Annals of hematology · 2025Article
- Comprehensive Characterization of Bruton's Tyrosine Kinase Inhibitor Specificity, Potency, and Biological Effects: Insights into Covalent and Noncovalent Mechanistic Signatures.ACS pharmacology & translational science · 2025Review
- From development to clinical success: the journey of established and next-generation BTK inhibitors.Investigational new drugs · 2025Review
- Review
- Review
- Bruton's Tyrosine Kinase (BTK) Mutations in Chronic Lymphocytic Leukemia (CLL): A Clinical View.Mediterranean journal of hematology and infectious diseases · 2025Review
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The covalent Bruton's tyrosine kinase inhibitors (BTKis) are highly effective for the treatment of chronic lymphocytic leukemia (CLL). The dominant resistance mechanism observed with the BTKi ibrutinib is the development of BTK Cys481 codon mutations. Whether a similar resistance mutation profile exists for the newer-generation, more selective BTKi zanubrutinib is unknown. In samples referred for diagnostic next-generation sequencing in patients with progressive CLL, we observed an enrichment in the kinase-dead BTK Leu528Trp mutation in patients treated with zanubrutinib compared with ibrutinib (54%; 7 of 13 vs 4%; 1 of 24, P = .001). We describe 2 patients with BTK Leu528Trp mutations who showed clinical cross-resistance and progressive enrichment of the BTK Leu528Trp mutation over time when treated with the noncovalent BTKi pirtobrutinib. Both patients subsequently responded to venetoclax-based treatment. In summary, we have identified an enrichment of the BTK Leu528Trp mutation arising in patients treated with zanubrutinib that may impart cross-resistance to the noncovalent inhibitor pirtobrutinib and therefore may have implications for sequencing of these treatments in CLL.
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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.