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December 8, 2025Blood

Genomic assessment of acquired mutations in participants with CLL/SLL treated with nemtabrutinib in the Phase 2 bellwave-003 study

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Authors

GPGuilherme Fleury PeriniCSChristof SchneiderMEMackenzie Edmondson

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Overview

Exploratory analysis reveals rare acquired resistance mutations in CLL/SLL patients treated with nemtabrutinib, suggesting potential for unique resistance profiles.

Key Points

  • To assess acquired mutations and response outcomes in CLL/SLL patients treated with nemtabrutinib.
  • Phase 2 BELLWAVE-003 study enrolled patients with R/R CLL/SLL for nemtabrutinib treatment.
  • Next-generation sequencing analyzed mutations in specific genes across treatment cycles.
  • Biomarker evaluable analysis included baseline and end-of-treatment samples.
  • Among 92 biomarker evaluable patients, 84 (88%) had mutations of interest at baseline.
  • Only 17 (18%) acquired new mutations post-treatment, primarily in TP53 and other poor prognosis genes.
  • No acquired BTK resistance mutations were detected in any patients by end of treatment.

Cite This Study

Perini et al. (2025) studied this question.

synapsesocial.com/papers/693624d74fa91c937236d08dhttps://doi.org/10.1182/blood-2025-797
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