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March 10, 2026American Journal of Hematology

Venetoclax or Pirtobrutinib in Relapsed/Refractory Waldenström Macroglobulinemia: Clinical and Molecular Predictors and Sequencing Implications

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Authors

AGAlberto GüijosaHarvard UniversityNTNickolas TsakamaklisDana-Farber Cancer InstituteMKMargaret KobsDana-Farber Cancer Institute

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Implication

Retrospective analysis compares venetoclax and pirtobrutinib efficacy in Waldenström macroglobulinemia, suggesting treatment sequencing implications.

Key Points

  • The study aims to evaluate the clinical effectiveness of venetoclax and pirtobrutinib in relapsed or refractory Waldenström macroglobulinemia while identifying relevant molecular predictors.
  • Retrospective evaluation of WM patients treated with venetoclax or pirtobrutinib.
  • Assessment of major response rate (MRR) and progression-free survival (PFS) for both agents.
  • Analysis of predictors using logistic and Cox regression models.
  • Comparison of efficacy in unmatched and 1:1 matched cohorts.
  • 19% of patients treated with venetoclax discontinued due to adverse effects, while none discontinued pirtobrutinib.
  • TP53 alterations correlated with shorter PFS in the venetoclax cohort.
  • CXCR4 mutations predicted lower MRR and shorter PFS in the pirtobrutinib cohort.
  • In the matched cohort, both agents showed comparable outcomes for MRR and PFS.

Cite This Study

Güijosa et al. (2026) studied this question.

synapsesocial.com/papers/69af952b70916d39fea4c621https://doi.org/10.1002/ajh.70269
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Also Consider

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

  1. 1Venetoclax or pirtobrutinib in relapsed/refractory Waldenström macroglobulinemia: Clinical and molecular predictors and sequencing implications2025 · 2 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 Macroglobulinemia2026
  4. 4Final report of a phase II study of ibrutinib and venetoclax in previously untreated Waldenström macroglobulinemia2025 · 1 citations
  5. 5Pirtobrutinib in Relapsed/Refractory (R/R) Waldenström macroglobulinemia (WM): Up to 5 years of follow-up from the Phase 1/2 BRUIN study2025 · 5 citations