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December 8, 2025BloodOpen Access

Clonal architecture and growth dynamics of ibrutinib-resistant CLL: Oligoclonal BTK/PLCG2 mutations and emerging non-BTK/PLCG2 drivers

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Authors

LVLauren VaughnPNPia Nierman

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Overview

Phase 2 study reveals progression-free survival in CLL with ibrutinib resistance, suggesting new genomic drivers.

Key Points

  • To examine clonal architecture and dynamics of progression in ibrutinib-resistant chronic lymphocytic leukemia.
  • Conducted a phase 2 study with 84 CLL patients on ibrutinib treatment.
  • Performed genotyping for hotspot mutations in BTK and PLCG2.
  • Conducted whole-exome sequencing and clonal decomposition analysis.
  • Calculated lymphocyte doubling time for resistant clones.
  • 89.7% of patients with progressive disease had detectable BTK/PLCG2 mutations.
  • Median progression-free survival was 86.6 months.
  • Identified potential alternative drivers of resistance beyond BTK/PLCG2 mutations.

Cite This Study

Vaughn et al. (2025) studied this question.

synapsesocial.com/papers/69362f4e4fa91c937236d8afhttps://doi.org/10.1182/blood-2025-5654
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Also Consider

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

  1. 1Abstract 5828: The genomic architecture of ibrutinib resistance in CLL: Oligoclonal progression with variable anatomical distribution2024
  2. 2Data from B-cell receptor pathway mutations are infrequent in patients with chronic lymphocytic leukemia on continuous ibrutinib therapy2024
  3. 3Genomic profiling in CLL patients after BTK inhibitor progression identifies enrichment of mutations in MAPK pathway and epigenetic regulators2025
  4. 4The mutational landscape of resistance to BTK and BCL2 inhibitors in CLL: a real-world multicentric study2026
  5. 5Acquired 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 patients2025 · 3 citations