A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study
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- Constantine S. Tam
- Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;
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- Stephen Opat
- Monash Health, Clayton, VIC, Australia;
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- Shirley D'Sa
- University College London Hospital Foundation Trust, London, United Kingdom;
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- Wojciech Jurczak
- Maria Sklodowska-Curie National Institute of Oncology, Krakow, Poland;
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- Hui-Peng Lee
- Flinders Medical Centre, Adelaide, SA, Australia;
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- Gavin Cull
- Sir Charles Gairdner Hospital, Perth, WA, Australia;
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- Roger G. Owen
- St James’s University Hospital, Leeds, United Kingdom;
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- Paula Marlton
- Department of Haematology, Princess Alexandra Hospital, Brisbane, QLD, Australia;
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- Björn E. Wahlin
- Unit of Hematology, Department of Medicine, Karolinska Universitetssjukhuset–Karolinska Institutet, Stockholm, Sweden;
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- Ramón Garcia Sanz
- Hospital Universitario de Salamanca, Salamanca, Spain;
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- Helen McCarthy
- Royal Bournemouth and Christchurch Hospital, Bournemouth, United Kingdom;
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- Stephen Mulligan
- Royal North Shore Hospital, Sydney, NSW, Australia;
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- Alessandra Tedeschi
- ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy;
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- Jorge J. Castillo
- Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
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- Jaroslaw Czyz
- Szpital Uniwersytecki No 2 im Dr Jana Biziela, Bydgoszcz, Poland;
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- Carlos Fernández de Larrea
- Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain;
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- David Belada
- Fourth Department of Internal Medicine - Haematology, Charles University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic;
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- Edward Libby
- Department of Medicine, University of Washington and the Seattle Cancer Care Alliance, Seattle, WA;
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- Jeffrey V. Matous
- Colorado Blood Cancer Institute, Denver, CO;
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- Marina Motta
- ASST Spedali Civili di Brescia, Lombardia, Italy;
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- Tanya Siddiqi
- City of Hope National Medical Center, Duarte, CA;
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- Monica Tani
- Ospedale Civile S Maria delle Croci, Azienda Unità Sanitaria Locale (AUSL), Ravenna, Italy;
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- Marek Trneny
- First Department of Medicine, First Faculty of Medicine, Charles University, General Hospital, Prague, Czech Republic;
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- Monique C. Minnema
- University Medical Center Utrecht, Utrecht, The Netherlands;
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- Christian Buske
- Comprehensive Cancer Center Ulm–Universitätsklinikum Ulm, Ulm, Germany;
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- Veronique Leblond
- Service d'Hématologie Clinique, Sorbonne University, Pitié Salpêtrière Hospital, Paris, France;
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- Judith Trotman
- Haematology Department, University of Sydney, Concord, NSW, Australia;
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- Wai Y. Chan
- BeiGene USA, Inc, San Mateo, CA; and
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- Jingjing Schneider
- BeiGene USA, Inc, San Mateo, CA; and
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- Sunhee Ro
- BeiGene USA, Inc, San Mateo, CA; and
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- Aileen Cohen
- BeiGene USA, Inc, San Mateo, CA; and
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- Jane Huang
- BeiGene USA, Inc, San Mateo, CA; and
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- Meletios Dimopoulos
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
抄録
<jats:title>Abstract</jats:title> <jats:p>Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P = .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.</jats:p>
収録刊行物
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- Blood
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Blood 136 (18), 2038-2050, 2020-10-29
American Society of Hematology