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Biomarker analysis of the ASPEN study comparing zanubrutinib with ibrutinib for patients with Waldenström macroglobulinemia
CS. Tam, S. Opat, S. D'Sa, W. Jurczak, HP. Lee, G. Cull, RG. Owen, P. Marlton, BE. Wahlin, R. García-Sanz, H. McCarthy, S. Mulligan, A. Tedeschi, JJ. Castillo, J. Czyż, C. Fernández De Larrea, D. Belada, E. Libby, J. Matous, M. Motta, T. Siddiqi,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
NLK
Directory of Open Access Journals
od 2016
PubMed Central
od 2016
Europe PubMed Central
od 2016
ROAD: Directory of Open Access Scholarly Resources
od 2016
- MeSH
- adenin analogy a deriváty MeSH
- biologické markery MeSH
- lidé MeSH
- myeloidní diferenciační faktor 88 genetika MeSH
- piperidiny * MeSH
- pyrazoly * MeSH
- pyrimidiny * MeSH
- Waldenströmova makroglobulinemie * farmakoterapie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The 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.
Amyloidosis and Myeloma Unit Department of Hematology Hospital Clínic de Barcelona Barcelona Spain
Bing Center for Waldenstrom Macroglobulinemia Dana Farber Cancer Institute Boston MA
Clinical Research Division Fred Hutchinson Cancer Center Seattle WA
Colorado Blood Cancer Institute Denver CO
Comprehensive Cancer Center Ulm Universitätsklinikum Ulm Ulm Baden Württemberg Germany
Department of Clinical Oncology Maria Sklodowska Curie National Institute of Oncology Krakow Poland
Department of Clinical Therapeutics National and Kapodistrian University of Athens Athens Greece
Department of Haematology Flinders Medical Centre Adelaide SA Australia
Department of Haematology Monash Health and Monash University Clayton VIC Australia
Department of Haematology Royal Bournemouth and Christchurch Hospital Bournemouth United Kingdom
Department of Haematology Royal North Shore Hospital Sydney NSW Australia
Department of Hematology AO Spedali Civili di Brescia Lombardia Italy
Department of Hematology Concord Repatriation General Hospital Sydney NSW Australia
Department of Hematology Hospital Universitario de Salamanca Salamanca Spain
Department of Hematology University Medical Center Utrecht Utrecht Netherlands
Haematological Malignancy Diagnostic Service St James University Hospital Leeds United Kingdom
Service d'Hématologie Clinique Sorbonne University Pitié Salpêtrière Hospital Paris France
Citace poskytuje Crossref.org
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