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December 8, 2025BloodOpen Access

Acquired Bruton's tyrosine kinase mutations in patients treated on the ibrutinib and rituximab, ibrutinib alone, and ibrutinib and venetoclax arms of the national multi-centre Phase III FLAIR study in previously untreated CLL patients

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Authors

NWNichola WebsterRTRuth de TuteSJSharon Jackson

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Overview

Phase III trial shows BTK mutations in 24% of patients treated with ibrutinib and rituximab, suggesting relapse factors remain.

Key Points

  • The research aims to analyze BTK mutations in CLL patients undergoing ibrutinib-containing treatments.
  • Peripheral blood DNA samples from patients with progressive disease were analyzed for BTK mutations.
  • Digital droplet PCR was employed to detect mutations at C481 and T474 hotspots.
  • Aliquot parameters like fractional abundance were utilized to assess allelic burden.
  • 24% of patients on ibrutinib and rituximab had BTK mutations at disease progression.
  • No mutations were found in patients treated with ibrutinib and venetoclax.
  • Mutations exhibited evolutionary dynamics, increasing during treatment and decreasing after cessation.

Cite This Study

Webster et al. (2025) studied this question.

synapsesocial.com/papers/693624d44fa91c937236d05chttps://doi.org/10.1182/blood-2025-796
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Clonal architecture and growth dynamics of ibrutinib-resistant CLL: Oligoclonal BTK/PLCG2 mutations and emerging non-BTK/PLCG2 drivers2025 · 1 citations
  2. 2Genomic profiling in CLL patients after BTK inhibitor progression identifies enrichment of mutations in MAPK pathway and epigenetic regulators2025
  3. 3Pirtobrutinib in Chronic Lymphocytic Leukemia: Navigating Resistance and the Personalisation of BTK-Targeted Therapy2025 · 4 citations
  4. 4Loss-of-function alterations in TRAF3 drive BTK/PLCG2-independent ibrutinib resistance in CLL2025
  5. 5Updates of R/R CLL with prior exposure to Bruton's tyrosine kinase (BTK) inhibitor and/or bcl-2 inhibitor in the Phase 1 trial of LP-168 (Rocbrutinib), a novel COVALENT and non-COVALENT BTK inhibitor2025 · 2 citations