Biomarker analysis of the ASPEN study comparing zanubrutinib with ibrutinib for patients with Waldenström macroglobulinemia

被引：12

作者：

Tam, Constantine S. ^{[1
,2
,36
,37
]}

Opat, Stephen ^{[3
,4
]}

D'Sa, Shirley ^{[5
]}

Jurczak, Wojciech ^{[6
]}

Lee, Hui-Peng ^{[7
]}

Cull, Gavin ^{[8
]}

Owen, Roger G. ^{[9
]}

Marlton, Paula ^{[10
,11
]}

Wahlin, Bjoern E. ^{[12
,13
]}

Garcia-Sanz, Ramon ^{[14
]}

McCarthy, Helen ^{[15
]}

Mulligan, Stephen ^{[16
]}

Tedeschi, Alessandra ^{[17
]}

Castillo, Jorge J. ^{[18
]}

Czyz, Jaros law ^{[19
]}

De Larrea, Carlos Fernandez ^{[20
]}

Belada, David ^{[21
,22
]}

Libby, Edward ^{[23
]}

Matous, Jeffrey ^{[24
]}

Motta, Marina ^{[25
]}

Siddiqi, Tanya ^{[26
]}

Tani, Monica ^{[27
]}

Trneny, Marek ^{[28
]}

Minnema, Monique C. ^{[29
]}

Buske, Christian ^{[30
]}

Leblond, Veronique ^{[31
]}

Treon, Steven P. ^{[18
]}

Trotman, Judith ^{[32
]}

Wu, Binghao ^{[33
,34
]}

Yu, Yiling ^{[33
,34
]}

Shen, Zhirong ^{[33
,34
]}

Chan, Wai Y. ^{[33
,34
]}

Schneider, Jingjing ^{[33
,34
]}

Allewelt, Heather ^{[33
,34
]}

Cohen, Aileen ^{[33
,34
]}

Dimopoulos, Meletios A. ^{[35
]}

机构：

[1] Alfred Hosp, Dept Haematol, Melbourne, VIC, Australia

[2] Monash Univ, Ctr Blood Dis, Melbourne, VIC, Australia

[3] Dept Haematol, Monash Hlth, Clayton, VIC, Australia

[4] Monash Univ, Clayton, VIC, Australia

[5] Univ Coll London Hosp Fdn Trust, Ctr Waldenstroms Macroglobulinemia & Associated Di, London, England

[6] Maria Sklodowska Curie Natl Inst Oncol, Dept Clin Oncol, Krakow, Poland

[7] Flinders Med Ctr, Dept Haematol, Adelaide, SA, Australia

[8] Univ Western Australia, Dept Haematol, University of Western Australia, Perth, WA, Australia

[9] St James Univ Hosp, Haematol Malignancy Diag Serv, Leeds, England

[10] Univ Queensland, Dept Haematol, Brisbane, QLD, Australia

[11] Univ Queensland, Brisbane, QLD, Australia

[12] Karolinska Univ Sjukhuset, Dept Hematol, Stockholm, Sweden

[13] Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden

[14] Hosp Univ Salamanca, Dept Hematol, Salamanca, Spain

[15] Royal Bournemouth & Christchurch Hosp, Dept Haematol, Bournemouth, England

[16] Royal North Shore Hosp, Dept Haematol, Sydney, NSW, Australia

[17] ASST Grande Osped Metropolitano Niguarda, Niguarda Canc Ctr, Dept Hematol, Milan, Italy

[18] Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA USA

[19] Nicolaus Copernicus Univ Torun, Dept Hematol, Coll Med Bydgoszcz, Bydgoszcz, Poland

[20] Hosp Clin Barcelona, Dept Hematol, Amyloidosis & Myeloma Unit, Barcelona, Spain

[21] Univ Hosp, Dept Internal Med Haematol, Hradec Kralove, Czech Republic

[22] Univ Hosp, Fac Med, Hradec Kralove, Czech Republic

[23] Fred Hutchinson Canc Ctr, Clin Res Div, Seattle, WA USA

[24] Colorado Blood Canc Inst, Denver, CO USA

[25] AO Spedali Civili Brescia, Dept Hematol, Lombardia, Italy

[26] City Hope Natl Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, Duarte, CA USA

[27] Ospedale Civile Santa Maria delle Croci, Osped Civile Santa Maria delle Croci, Dipartimento Oncol & Ematol, Dipartimento Oncologia e Ematologia, Ravenna, Italy

[28] Vseobecna Fak Nemocnice Praze, Prague, Czech Republic

[29] Univ Med Ctr Utrecht, Dept Hematol, Utrecht, Netherlands

[30] Univ Klinikum Ulm, Comprehens Canc Ctr Ulm, Ulm, Baden Wurttembe, Germany

[31] Sorbonne Univ, Pitie Salpetriere Hosp, Serv Hematol Clin, Paris, France

[32] Concord Repatriat Gen Hosp, Dept Haematol, Sydney, NSW, Australia

[33] BeiGene USA Inc, San Mateo, CA USA

[34] BeiGene Shanghai Co Ltd, Shanghai, Peoples R China

[35] Natl & Kapodistrian Univ Athens, Dept Clin Therapeut, Athens, Greece

[36] Alfred Hlth, 55 Commercial Rd, East Melbourne, VIC 3004, Australia

[37] Monash Univ, 55 Commercial Rd, East Melbourne, VIC 3004, Australia

来源：

BLOOD ADVANCES | 2024年 / 8卷 / 07期

关键词：

WALDENSTROM MACROGLOBULINEMIA; MUTATIONS; MYD88; RESISTANCE; SURVIVAL; CXCR4; CELLS;

D O I：

10.1182/bloodadvances.2023010906

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The phase 3 ASPEN trial (NCT03053440) compared Bruton tyrosine kinase inhibitors (BTKis), zanubrutinib and ibrutinib, in patients with Waldenstr & ouml;m 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. TP53(MUT), ARID1A(MUT), and TERTMUT were associated with higher rates of CXCR4(MUT) (P < .05). Patients with CXCR4(MUT) (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 CXCR4(WT) treated with BTKis. CXCR4(NS) 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 CXCR4(NS) 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 TP53(MUT), 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 TP53(MUT), 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 CXCR4(MUT) or TP53(MUT) had worse prognosis compared with patients with WT alleles, and zanubrutinib led to better clinical outcomes.

引用

页码：1639 / 1650

页数：12

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