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Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial
M. Dimopoulos, RG. Sanz, HP. Lee, M. Trneny, M. Varettoni, S. Opat, S. D'Sa, RG. Owen, G. Cull, S. Mulligan, J. Czyz, JJ. Castillo, M. Motta, T. Siddiqi, M. Gironella Mesa, M. Granell Gorrochategui, D. Talaulikar, PL. Zinzani, E. Askari, S....
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
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- MeSH
- Humans MeSH
- Myeloid Differentiation Factor 88 * genetics MeSH
- Piperidines MeSH
- Pyrazoles adverse effects MeSH
- Pyrimidines adverse effects MeSH
- Waldenstrom Macroglobulinemia * drug therapy genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Patients with Waldenström macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients with WM who have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88WT) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/refractory; 5 treatment-naïve) were enrolled, including 26 with centrally confirmed MYD88WT disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88WT patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88WT WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440.
AO Spedali Civili di Brescia Lombardia Italy
ASST Grande Ospedale Metropolitano Niguarda Milan Italy
Azienda Ospedaliero Universitaria di Bologna Bologna Italy
BeiGene Switzerland GmbH Basel Switzerland
Bing Center for Waldenström Macroglobulinemia Dana Farber Cancer Institute Boston MA
City of Hope National Medical Center Duarte CA
Clinical Hematology Department Sorbonne University Pitié Salpêtrière Hospital Paris France
Comprehensive Cancer Center Ulm Universitätsklinikum Ulm Baden Württemberg Germany
Concord Repatriation General Hospital Sydney Concord NSW Australia
Department of Clinical Therapeutics National and Kapodistrian University of Athens Athens Greece
Department of Haematology Flinders Medical Centre Adelaide SA Australia
Department of Hematology School of Clinical Sciences Monash University Clayton VIC Australia
Faculty of Medicine Dentistry and Health Sciences University of Melbourne Parkville VIC Australia
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Pavia Italy
Hospital de La Santa Creu i Sant Pau Barcelona Spain
Hospital Universitario de Salamanca Salamanca Spain
Hospital Universitario Fundación Jiménez Díaz Madrid Spain
Hospital Universitario Vall d'Hebrón Barcelona Spain
Institut Català d'Oncologia Hospital Universitari Germans Trias i Pujol Barcelona Spain
Medical Oncology Harvard Medical School Boston MA
Pathology and Laboratory Medicine University of Western Australia Perth WA Australia
Peter MacCallum Cancer Centre Melbourne VIC Australia
Plymouth Hospitals National Health Service Trust Derriford Hospital Devon United Kingdom
Royal Melbourne Hospital Parkville VIC Australia
Royal North Shore Hospital Sydney NSW Australia
Sir Charles Gairdner Hospital Perth WA Australia
St James University Hospital Leeds United Kingdom
St Vincent's Hospital Fitzroy VIC Australia
Szpital Uniwersytecki nr 2 Dr Jana Biziela Kujawsko pomorskie Bydgoszcz Poland
The John Curtin School of Medical Research Australian National University Canberra ACT Australia
University College London Hospital Foundation Trust London United Kingdom
Uniwersytecki Szpital Kliniczny w Bialymstoku Podlaskie Poland
References provided by Crossref.org
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