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Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial
S. Grosicki, M. Simonova, I. Spicka, L. Pour, I. Kriachok, M. Gavriatopoulou, H. Pylypenko, HW. Auner, X. Leleu, V. Doronin, G. Usenko, NJ. Bahlis, R. Hajek, R. Benjamin, TK. Dolai, DK. Sinha, CP. Venner, M. Garg, M. Gironella, A. Jurczyszyn, P....
Language English Country Great Britain
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 1992-01-04 to 3 months ago
Nursing & Allied Health Database (ProQuest)
from 1992-01-04 to 3 months ago
Health & Medicine (ProQuest)
from 1992-01-04 to 3 months ago
Family Health Database (ProQuest)
from 1992-01-04 to 3 months ago
Psychology Database (ProQuest)
from 1992-01-04 to 3 months ago
Health Management Database (ProQuest)
from 1992-01-04 to 3 months ago
Public Health Database (ProQuest)
from 1992-01-04 to 3 months ago
- MeSH
- Antineoplastic Agents administration & dosage adverse effects MeSH
- Bortezomib administration & dosage adverse effects MeSH
- Dexamethasone administration & dosage adverse effects MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Hydrazines administration & dosage adverse effects MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Multiple Myeloma drug therapy MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects MeSH
- Drug Administration Schedule MeSH
- Aged MeSH
- Triazoles administration & dosage adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. We aimed to evaluate the clinical benefit of weekly selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone in patients with previously treated multiple myeloma. METHODS: This phase 3, randomised, open-label trial was done at 123 sites in 21 countries. Patients aged 18 years or older, who had multiple myeloma, and who had previously been treated with one to three lines of therapy, including proteasome inhibitors, were randomly allocated (1:1) to receive selinexor (100 mg once per week), bortezomib (1·3 mg/m2 once per week), and dexamethasone (20 mg twice per week), or bortezomib (1·3 mg/m2 twice per week for the first 24 weeks and once per week thereafter) and dexamethasone (20 mg four times per week for the first 24 weeks and twice per week thereafter). Randomisation was done using interactive response technology and stratified by previous proteasome inhibitor therapy, lines of treatment, and multiple myeloma stage. The primary endpoint was progression-free survival in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. The trial is ongoing, with 55 patients remaining on randomised therapy as of Feb 20, 2020. FINDINGS: Of 457 patients screened for eligibility, 402 were randomly allocated-195 (49%) to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group-and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13·2 months [IQR 6·2-19·8] for the selinexor, bortezomib, and dexamethasone group and 16·5 months [9·4-19·8] for the bortezomib and dexamethasone group. Median progression-free survival was 13·93 months (95% CI 11·73-not evaluable) with selinexor, bortezomib, and dexamethasone and 9·46 months (8·11-10·78) with bortezomib and dexamethasone (hazard ratio 0·70 [95% CI 0·53-0·93], p=0·0075). The most frequent grade 3-4 adverse events were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs two [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; odds ratio 0·50 [95% CI 0·32-0·79], p=0·0013). 47 (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died. INTERPRETATION: A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy. FUNDING: Karyopharm Therapeutics.
Alexandra Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece
Azienda Ospedaliero Universitaria di Bologna Bologna Italy
Baylor University Medical Center Dallas TX USA
Bone Marrow Transplantation Department Kyiv Bone Marrow Transplantation Center Kyiv Ukraine
Charbonneau Cancer Research Institute University of Calgary Calgary AB Canada
Charles University and General Hospital Prague Czech Republic
CHU Lille Service des Maladies du Sang F 59000 Lille France
City Clinical Hospital 4 of Dnipro City Council City Hematology Center Dnipro Ukraine
City Clinical Hospital No 40 Moscow Russia
Clinic for Hematology Clinical Centre of Serbia Belgrade Serbia
Clinic of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic
Cross Cancer Institute University of Alberta Edmonton AB Canada
Dana Farber Cancer Institute Boston MA USA
Department of Hematology Cherkassy Regional Oncological Center Cherkassy Ukraine
Department of Hematology CHU la Miletrie and Inserm CIC 1402 Poitiers France
Department of Hematology Copernicus Memorial Hospital Medical University of Lodz Lodz Poland
Department of Hematology Jagiellonian University Medical College Kraków Poland
Department of Hematology Vinnytsia M 1 Pyrohov Regional Clinical Hospital Vinnytsia Ukraine
Department of Oncology and Hematology Papa Giovanni XXIII Hospital Bergamo Italy
Flinders Medical Centre and Flinders University Adelaide SA Australia
General Hospital Evangelismos Athens Greece
Hadassah Hebrew University Medical Center Jerusalem Israel
Hematology Department Theagenion Cancer Hospital Thessaloniki Greece
Hospital Universitario de Salamanca Salamanca Spain
Imperial College London London UK
Karyopharm Therapeutics Newton MA USA
Kings College NHS Foundation Trust Kings College London London UK
Medical University of Silesia Katowice Poland
National Cancer Institute Ukraine Kiev Ukraine
New Cross Hospital Royal Wolverhampton NHS Trust and University of Wolverhampton Wolverhampton UK
Nil Ratan Sircar Medical College and Hospital Kolkata India
Norton Cancer Institute St Matthews Campus Louisville KY USA
Oncohematology Hospital S Maria Terni University of Perugia Terni Italy
Queen Elizabeth 2 Health Sciences Centre Dalhousie University Halifax NS Canada
School of Medicine National and Kapodistrian University of Athens Athens Greece
Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center Dallas TX USA
State Cancer Institute Indira Gandhi Institute of Medical Sciences Patna India
Tata Medical Center Kolkata India
Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY USA
University Health Network Princess Margaret Cancer Centre Toronto ON Canada
University Hospital Hotel Dieu Nantes France
University Hospital St Ivan Rilski EAD Sofia Bulgaria
University Hospitals of Leicester NHS Trust Leicester UK
University of Melbourne St Vincent's Hospital Melbourne VIC Australia
References provided by Crossref.org
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