학술논문
Biomarker analysis of the ASPEN study comparing zanubrutinib with ibrutinib for patients with Waldenström macroglobulinemia.
Document Type
Academic Journal
Author
Tam CS; Department of Haematology, Alfred Hospital and Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.; Opat S; Department of Haematology, Monash Health and Monash University, Clayton, VIC, Australia.; D'Sa S; Centre for Waldenström's Macroglobulinemia and Associated Disorders, University College London Hospital Foundation Trust, London, United Kingdom.; Jurczak W; Department of Clinical Oncology, Maria Sklodowska-Curie National Institute of Oncology, Krakow, Poland.; Lee HP; Department of Haematology, Flinders Medical Centre, Adelaide, SA, Australia.; Cull G; Department of Haematology, Sir Charles Gairdner Hospital, University of Western Australia, Perth, WA, Australia.; Owen RG; Haematological Malignancy Diagnostic Service, St James University Hospital, Leeds, United Kingdom.; Marlton P; Department of Haematology, Princess Alexandra Hospital and University of Queensland, Brisbane, QLD, Australia.; Wahlin BE; Department of Hematology, Karolinska Universitetssjukhuset and Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.; García-Sanz R; Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain.; McCarthy H; Department of Haematology, Royal Bournemouth and Christchurch Hospital, Bournemouth, United Kingdom.; Mulligan S; Department of Haematology, Royal North Shore Hospital, Sydney, NSW, Australia.; Tedeschi A; Department of Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.; Castillo JJ; Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA.; Czyż J; Department of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.; Fernández De Larrea C; Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.; Belada D; Department of Internal Medicine - Haematology, University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic.; Libby E; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.; Matous J; Colorado Blood Cancer Institute, Denver, CO.; Motta M; Department of Hematology, AO Spedali Civili di Brescia, Lombardia, Italy.; Siddiqi T; Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA.; Tani M; U.O. Ematologia, Dipartimento Oncologia e Ematologia, Ospedale Civile Santa Maria delle Croci, AUSL Ravenna, Italy.; Trněný M; Všeobecná fakultní nemocnice v Praze, Prague, Czechia.; Minnema MC; Department of Hematology, University Medical Center Utrecht, Utrecht, Netherlands.; Buske C; Comprehensive Cancer Center Ulm, Universitätsklinikum Ulm, Ulm, Baden-Württemberg, Germany.; Leblond V; Service d'Hématologie Clinique, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France.; Treon SP; Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA.; Trotman J; Department of Hematology, Concord Repatriation General Hospital, Sydney, NSW, Australia.; Wu B; BeiGene USA, Inc, San Mateo, CA.; BeiGene Co, Ltd, Shanghai, China.; Yu Y; BeiGene USA, Inc, San Mateo, CA.; BeiGene Co, Ltd, Shanghai, China.; Shen Z; BeiGene USA, Inc, San Mateo, CA.; BeiGene Co, Ltd, Shanghai, China.; Chan WY; BeiGene USA, Inc, San Mateo, CA.; BeiGene Co, Ltd, Shanghai, China.; Schneider J; BeiGene USA, Inc, San Mateo, CA.; BeiGene Co, Ltd, Shanghai, China.; Allewelt H; BeiGene USA, Inc, San Mateo, CA.; BeiGene Co, Ltd, Shanghai, China.; Cohen A; BeiGene USA, Inc, San Mateo, CA.; BeiGene Co, Ltd, Shanghai, China.; Dimopoulos MA; Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece.
Source
Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
Subject
Language
English
Abstract
Abstract: 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.
(© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
(© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)