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August 30, 2026Experimental Hematology and OncologyOpen Access

Novel agents and evolving strategies in Waldenström macroglobulinemia: clinical trial updates from ASH 2025

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Authors

YLYaohua LiangJiujiang UniversityXDXinyi DengAnhui Agricultural UniversityZWZiwen WangSun Yat-sen University

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Implication

Clinical trial review reveals emerging targeted therapies in Waldenström macroglobulinemia, indicating viable options to overcome covalent BTK inhibitor resistance.

Key Points

  • Summarize emerging clinical trial data presented at ASH 2025 evaluating novel therapeutics designed to overcome drug resistance and enhance treatment durability in Waldenström macroglobulinemia.
  • Synthesized clinical trial reports presented at the 2025 American Society of Hematology Annual Meeting.
  • Evaluated frontline immunochemotherapy combinations as well as novel targeted agents in relapsed or refractory disease settings.
  • Non-covalent BTK inhibitors and BTK protein degraders demonstrated therapeutic capability to circumvent acquired C481S resistance mutations.
  • Emerging chemotherapy-free options, including BCL2 inhibitors, MALT1 inhibitors, and CD19-directed antibody-drug conjugates and cellular therapies, showed promising activity across resistant cohorts.

Cite This Study

Liang et al. (2026) studied this question.

synapsesocial.com/papers/6a93f1056c1a8fb52e79db53https://doi.org/10.1186/s40164-026-00821-0
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Also Consider

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

  1. 1Deep responses following treatment with loncastuximab tesirine (WM-NET1 trial) in patients with Relapsed/Refractory including those withhigh-risk, TP53-altered Waldenström macroglobulinemia.2025 · 3 citations
  2. 2High VGPR/CR rates with pirtobrutinib plus venetoclax in previously treated Waldenström macroglobulinemia: Results from a multicenter phase II study2025 · 5 citations
  3. 3Final report of a phase II study of ibrutinib and venetoclax in previously untreated Waldenström macroglobulinemia2025 · 1 citations
  4. 4Updated efficacy and safety results of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed/refractory Waldenström macroglobulinemia from the ongoing phase 1 CaDAnCe-101 study2025 · 5 citations
  5. 5Bexobrutideg (NX-5948), a novel Bruton's tyrosine kinase (BTK) degrader, shows high clinical activity and tolerable safety in patients with Waldenström macroglobulinemia: Updated results from an ongoing Phase 1a/b study2025 · 4 citations