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Title: | A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenstrom macroglobulinemia: The ASPEN study. | Authors: | Sanz R.G.;Tam C.S.;Opat S. ;D'Sa S.;Jurczak W.;Lee H.-P.;Cull G.;Owen R.G.;Marlton P.;Ewahlin B.;Motta M.;Siddiqi T.;Tani M.;Trneny M.;Minnema M.C.;Buske C.;Leblond V.;Trotman J.;Chan W.Y.;Schneider J.;Ro S.;Cohen A.;Huang J.;McCarthy H.;Mulligan S.;Tedeschi A.;Castillo J.J.;Czyz J.;De Larrea C.F.;Belada D.;Libby E.;Matous J.V. | Institution: | (Tam) Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (D'Sa) St Vincent's Hospital, Fitzroy, VIC, Australia (Jurczak) Department of Medicine, University of Melbourne, Parkville, VIC, Australia (Tam) Royal Melbourne Hospital, Parkville, VIC, Australia (Opat) Monash Health, Clayton, VIC, Australia (Opat) Clinical Haematology Unit, Monash University, Clayton, VIC, Australia (D'Sa) University College London Hospital Foundation Trust, London, United Kingdom (Jurczak) Maria Sklodowska-Curie National Institute of Oncology, Krakow, Poland (Lee) Flinders Medical Centre, Adelaide, SA, Australia (Cull) Sir Charles Gairdner Hospital, Perth, WA, Australia (Cull) Department of Lymphoma/Myeloma, University of Western Australia, Perth, WA, Australia (Owen) St James's University Hospital, Leeds, United Kingdom (Marlton) Department of Haematology, Princess Alexandra Hospital, Brisbane, QLD, Australia (Marlton) School of Medicine, University of Queensland, Brisbane, QLD, Australia (Ewahlin) Department of Medicine, Unit of Hematology, Karolinska Universitetssjukhuset-Karolinska Institutet, Stockholm, Sweden (Sanz) Hospital Universitario de Salamanca, Salamanca, Spain (McCarthy) United Kingdom, Royal Bournemouth and Christchurch Hospital, Bournemouth, United Kingdom (Mulligan) Royal North Shore Hospital, Sydney, NSW, Australia (Tedeschi) Asst Grande Ospedale Metropolitano Niguarda, Milan, Italy (Castillo) Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, United States (Castillo) Department of Medicine, Harvard Medical School, Boston, MA, United States (Czyz) Szpital Uniwersytecki No 2 im Dr Jana Biziela, Bydgoszcz, Poland (Czyz) Department of Hematology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland (De Larrea) August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic of Barcelona, Amyloidosis and Myeloma Unit, Barcelona, Spain (Belada) Fourth Department of Internal Medicine-Haematology, Charles University Hospital and Faculty of Medicine, Hradec Kralove, Czechia (Libby) Department of Medicine, University of Washington and Seattle Cancer Care Alliance, Seattle, WA, United States (Matous) Colorado Blood Cancer Institute, Denver, CO, United States (Motta) Asst Spedali Civili di Brescia, Lombardia, Italy (Siddiqi) City of Hope National Medical Center, Duarte, CA, United States (Tani) Azienda Unita Sanitaria Locale (AUSL), Ospedale Civile SMaria Delle Croci, Ravenna, Italy (Trneny) First Department of Medicine, Charles University, General Hospital, Prague, Czechia (Minnema) University Medical Center Utrecht, Utrecht, Netherlands (Buske) Comprehensive Cancer Center Ulm, Universita Tsklinikum Ulm, Ulm, Germany (Leblond) Service d'Hematologie Clinique, Sorbonne University, Pitie Salpe Trie Re Hospital, Paris, France (Trotman) Haematology Department, University of Sydney, Concord, NSW, Australia (Trotman) Department of Haematology, Concord Repatriation General Hospital, Sydney, Concord, NSW, Australia (Chan, Schneider, Ro, Cohen) BeiGene USA, Inc, San Mateo, CA, United States (Huang) Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece | Issue Date: | 31-Mar-2021 | Copyright year: | 2020 | Publisher: | American Society of Hematology | Place of publication: | United States | Publication information: | Blood. 136 (18) (pp 2038-2050), 2020. Date of Publication: 29 Oct 2020. | Journal: | Blood | Abstract: | Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenstrom 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 5 .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.Copyright © 2020 American Society of Hematology. All rights reserved. | DOI: | http://monash.idm.oclc.org/login?url= http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1182/BLOOD.2020006844 |
PubMed URL: | 32731259 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32731259] | ISSN: | 0006-4971 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/26832 | Type: | Article | Subjects: | nausea/si [Side Effect] neutropenia nuclear magnetic resonance imaging open study overall survival patient-reported outcome peripheral edema peripheral neuropathy/si [Side Effect] phase 3 clinical trial pneumonia priority journal progression free survival quality of life quantitative analysis randomized controlled trial rash/si [Side Effect] sepsis/si [Side Effect] skin cancer/si [Side Effect] subdural hematoma/si [Side Effect] thrombocytopenia/si [Side Effect] treatment duration treatment interruption treatment response tumor lysis syndrome/si [Side Effect] tumor volume upper respiratory tract infection/si [Side Effect] urinary tract infection/si [Side Effect] vomiting/si [Side Effect] *Waldenstroem macroglobulinemia/di [Diagnosis] *Waldenstroem macroglobulinemia/dm [Disease Management] *Waldenstroem macroglobulinemia/dt [Drug Therapy] beta 2 microglobulin/ec [Endogenous Compound] chemokine receptor CXCR4/ec [Endogenous Compound] hemoglobin/ec [Endogenous Compound] *ibrutinib/ae [Adverse Drug Reaction] *ibrutinib/ct [Clinical Trial] *ibrutinib/cm [Drug Comparison] *ibrutinib/dt [Drug Therapy] *ibrutinib/pd [Pharmacology] *ibrutinib/pv [Special Situation for Pharmacovigilance] immunoglobulin A/ec [Endogenous Compound] immunoglobulin G/ec [Endogenous Compound] immunoglobulin M/ec [Endogenous Compound] myeloid differentiation factor 88/ec [Endogenous Compound] *zanubrutinib/ae [Adverse Drug Reaction] *zanubrutinib/ct [Clinical Trial] *zanubrutinib/cm [Drug Comparison] *zanubrutinib/dt [Drug Therapy] *zanubrutinib/pd [Pharmacology] *zanubrutinib/pv [Special Situation for Pharmacovigilance] immunoglobulin A multiple myeloma/si [Side Effect] computer assisted tomography backache/si [Side Effect] bacteremia/si [Side Effect] blood viscosity bone marrow biopsy *cancer chemotherapy cohort analysis comorbidity adverse drug reaction/si [Side Effect] aged anemia/si [Side Effect] arthralgia/si [Side Effect] article *comparative effectiveness atrial fibrillation/si [Side Effect] constipation/si [Side Effect] contrast enhancement controlled study contusion diarrhea drug induced disease/si [Side Effect] *drug safety dyspnea/si [Side Effect] European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 fatigue/si [Side Effect] female fever/si [Side Effect] headache/si [Side Effect] heart arrest/si [Side Effect] heart infarction/si [Side Effect] hematuria/si [Side Effect] hemoglobin blood level hemoglobin determination hepatitis/si [Side Effect] high throughput sequencing human hypertension/si [Side Effect] interstitial lung disease/si [Side Effect] liver injury/si [Side Effect] major clinical study male Mantel Haenszel test missense mutation multiple myeloma/si [Side Effect] muscle spasm *comparative effectiveness computer assisted tomography constipation / side effect contrast enhancement controlled study contusion diarrhea drug induced disease / side effect *drug safety dyspnea / side effect European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 fatigue / side effect female fever / side effect headache / side effect heart arrest / side effect heart infarction / side effect hematuria / side effect hemoglobin blood level hemoglobin determination hepatitis / side effect high throughput sequencing human hypertension / side effect interstitial lung disease / side effect liver injury / side effect major clinical study male Mantel Haenszel test missense mutation multiple myeloma / side effect muscle spasm nausea / side effect neutropenia nuclear magnetic resonance imaging open study overall survival patient-reported outcome peripheral edema peripheral neuropathy / side effect phase 3 clinical trial pneumonia priority journal progression free survival quality of life arthralgia / side effect randomized controlled trial rash / side effect sepsis / side effect skin cancer / side effect subdural hematoma / side effect thrombocytopenia / side effect treatment duration treatment interruption treatment response tumor lysis syndrome / side effect tumor volume upper respiratory tract infection / side effect urinary tract infection / side effect vomiting / side effect *Waldenstroem macroglobulinemia / *diagnosis / *disease management / *drug therapy anemia / side effect aged adverse drug reaction / side effect quantitative analysis Article atrial fibrillation / side effect backache / side effect bacteremia / side effect blood viscosity bone marrow biopsy *cancer chemotherapy cohort analysis comorbidity |
Type of Clinical Study or Trial: | Randomised controlled trial |
Appears in Collections: | Articles |
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