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This is a Human Clinical Trial study (also classified as: Pre-Registered Trial).

December 8, 2025BloodOpen Access

Venetoclax or pirtobrutinib in relapsed/refractory Waldenström macroglobulinemia: Clinical and molecular predictors and sequencing implications

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Retrospective analysis shows venetoclax and pirtobrutinib yield comparable outcomes in relapsed Waldenström, highlighting TP53 status as a predictor.

To analyze the efficacy of venetoclax versus pirtobrutinib in relapsed/refractory Waldenström macroglobulinemia and identify predictors of response.
Retrospective analysis of WM patients treated with venetoclax or pirtobrutinib.
Responses assessed using IWWM-11 criteria.
Cohorts analyzed for major response rate (MRR) and progression-free survival (PFS).
Comparative efficacy evaluated with unmatched and 1:1 matched cohorts based on therapy history.
Factors impacting MRR and PFS were analyzed using multivariate methods.
Both venetoclax and pirtobrutinib showed comparable MRR (69% vs. 64%; p=0.63).
TP53 mutations predicted lower MRR with venetoclax (82% vs. 45%; p=0.02).
CXCR4 mutations predicted lower MRR with pirtobrutinib (40% vs. 91%; p=0.013).
Longer median PFS was linked to absence of TP53 mutations and fewer prior lines of therapy.
Median PFS was 32 months for venetoclax compared to 16 months for pirtobrutinib, favoring venetoclax, but not statistically significant (p=0.16).

Güijosa et al. (2025) studied this question.

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December 8, 2025BloodOpen Access

View Full Paper

Ask AI

Bookmark

Authors

Retrospective analysis shows venetoclax and pirtobrutinib yield comparable outcomes in relapsed Waldenström, highlighting TP53 status as a predictor.

To analyze the efficacy of venetoclax versus pirtobrutinib in relapsed/refractory Waldenström macroglobulinemia and identify predictors of response.
Retrospective analysis of WM patients treated with venetoclax or pirtobrutinib.
Responses assessed using IWWM-11 criteria.
Cohorts analyzed for major response rate (MRR) and progression-free survival (PFS).
Comparative efficacy evaluated with unmatched and 1:1 matched cohorts based on therapy history.
Factors impacting MRR and PFS were analyzed using multivariate methods.
Both venetoclax and pirtobrutinib showed comparable MRR (69% vs. 64%; p=0.63).
TP53 mutations predicted lower MRR with venetoclax (82% vs. 45%; p=0.02).
CXCR4 mutations predicted lower MRR with pirtobrutinib (40% vs. 91%; p=0.013).
Longer median PFS was linked to absence of TP53 mutations and fewer prior lines of therapy.
Median PFS was 32 months for venetoclax compared to 16 months for pirtobrutinib, favoring venetoclax, but not statistically significant (p=0.16).

Güijosa et al. (2025) studied this question.

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