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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 shows rare resistance mutations in CLL/SLL, suggesting unique mechanisms with nemtabrutinib.

Key Points

  • To explore mutations in CLL/SLL patients treated with nemtabrutinib and assess resistance mechanisms.
  • Phase 2 BELLWAVE-003 study enrolled relapsed/refractory CLL/SLL patients.
  • Next-generation sequencing performed on >400 cancer-related genes.
  • Identified baseline and end of treatment mutations associated with resistance and prognosis.
  • 84% of patients had one or more resistance or poor prognosis mutations at baseline.
  • 18% acquired mutations associated with poor prognosis post-treatment, with no canonical BTK resistance mutations detected.
  • The majority responded positively, with 67% achieving at least a partial response.

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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Also Consider

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

  1. 1Phase 2 bellwave-003 cohort f: Updated clinical outcomes of nemtabrutinib in participants with relapsed or refractory marginal zone lymphoma2025 · 1 citations
  2. 2BELLWAVE-011: Phase 3 randomized trial of nemtabrutinib versus ibrutinib or acalabrutinib in untreated chronic lymphocytic leukemia/small lymphocytic lymphoma.2024 · 5 citations
  3. 3BELLWAVE-010: A phase 3 study of nemtabrutinib plus venetoclax versus venetoclax plus rituximab (VR) in previously treated patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).2024
  4. 4Genomic profiling in CLL patients after BTK inhibitor progression identifies enrichment of mutations in MAPK pathway and epigenetic regulators2025
  5. 5Population Pharmacokinetic Modeling and Exposure-Response Analyses of Nemtabrutinib in Patients With Hematologic Malignancies.2026