ArticleBlood advances2024
Biomarker analysis of the ASPEN study comparing zanubrutinib with ibrutinib for patients with Waldenström macroglobulinemia.
Article in Blood advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03053440 (A Phase 3, Randomized, Open-Label, Multicenter Study Comparing the Efficacy and Safety of the Bruton's Tyrosine Kinase), which is not on this map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3, Randomized, Open-Label, Multicenter Study Comparing the Efficacy and Safety of the Bruton's Tyrosine Kinase (BTK) Inhibitors BGB-3111 and Ibrutinib in Subjects With Waldenström's Macroglobulinemia (WM)
Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Acalabrutinib in Waldenström macroglobulinemia yields durable responses with 5 years of follow-up.Blood advances · 2026Trial
- Trial
- Ibrutinib plus rituximab vs ibrutinib monotherapy in patients with Waldenström macroglobulinemia: a pooled analysis.Blood advances · 2025Trial
- Six-year follow-up of phase II study exploring chemo-free treatment association with idelalisib and obinutuzumab in symptomatic relapsed/ refractory patients with Waldenström's macroglobulinemia.Annals of hematology · 2025Trial
- Decoding Waldenström Macroglobulinemia Through Genomics, Epigenomics and Cellular Interactions.International journal of molecular sciences · 2026Review
- Article
- Refining prognostic tools in Waldenström macroglobulinemia.Blood advances · 2026Article
- Off-trial outcomes of zanubrutinib in Waldenström macroglobulinemia: the prognostic impact of CXCR4 and TP53 alterations.Leukemia · 2026Article
- Zanubrutinib in B-cell lymphomas: from clinical pharmacology to therapeutic application.European journal of clinical pharmacology · 2026Review
- Zanubrutinib in the treatment of Waldenström Macroglobulinemia.Future oncology (London, England) · 2025Review
- Waldenström Macroglobulinemia: The Role of TP53 Mutations in Disease Progression and Therapeutic Response.Current issues in molecular biology · 2025Review
- Article
- Efficacy and safety of chimeric antigen receptor T cell therapy combined with zanubrutinib in the treatment of relapsed/refractory diffuse large B-cell lymphoma.Chinese medical journal · 2025Article
- Case report: Therapeutic use of bortezomib in a patient with Schnitzler syndrome.Frontiers in immunology · 2025Article
- How I use genomics and BTK inhibitors in the treatment of Waldenström macroglobulinemia.Blood · 2024Article
Corrections and comments
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Authors and funding
36 authors at 20 institutions in 13 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
abstractThe phase 3 ASPEN trial (NCT03053440) compared Bruton tyrosine kinase inhibitors (BTKis), zanubrutinib and ibrutinib, in patients with Waldenström macroglobulinemia (WM). Post-hoc biomarker analysis was performed using next-generation sequencing on pretreatment bone marrow samples from 98 patients treated with zanubrutinib and 92 patients treated with ibrutinib with mutated (MUT) MYD88 and 20 patients with wild-type (WT) MYD88 treated with zanubrutinib. Of 329 mutations in 52 genes, mutations in CXCR4 (25.7%), TP53 (24.8%), ARID1A (15.7%), and TERT (9.0%) were most common. TP53MUT, ARID1AMUT, and TERTMUT were associated with higher rates of CXCR4MUT (P < .05). Patients with CXCR4MUT (frameshift or nonsense [NS] mutations) had lower very good partial response (VGPR) and complete response rates (CR; 17.0% vs 37.2%, P = .020) and longer time to response (11.1 vs 8.4 months) than patients with CXCR4WT treated with BTKis. CXCR4NS was associated with inferior progression-free survival (PFS; hazard ratio [HR], 3.39; P = .017) in patients treated with ibrutinib but not in those treated with zanubrutinib (HR, 0.67; P = .598), but VGPR + CR rates were similar between treatment groups (14.3% vs 15.4%). Compared with ibrutinib, patients with CXCR4NS treated with zanubrutinib had a favorable major response rate (MRR; 85.7% vs 53.8%; P = .09) and PFS (HR, 0.30; P = .093). In patients with TP53MUT, significantly lower MRRs were observed for patients treated with ibrutinib (63.6% vs 85.7%; P = .04) but not for those treated with zanubrutinib (80.8% vs 81.9%; P = .978). In TP53MUT, compared with ibrutinib, patients treated with zanubrutinib had higher VGPR and CR (34.6% vs 13.6%; P < .05), numerically improved MRR (80.8% vs 63.6%; P = .11), and longer PFS (not reached vs 44.2 months; HR, 0.66; P = .37). Collectively, patients with WM with CXCR4MUT or TP53MUT had worse prognosis compared with patients with WT alleles, and zanubrutinib led to better clinical outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.