• Je něco špatně v tomto záznamu ?

Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial

MV. Mateos, M. Cavo, J. Blade, MA. Dimopoulos, K. Suzuki, A. Jakubowiak, S. Knop, C. Doyen, P. Lucio, Z. Nagy, L. Pour, M. Cook, S. Grosicki, A. Crepaldi, AM. Liberati, P. Campbell, T. Shelekhova, SS. Yoon, G. Iosava, T. Fujisaki, M. Garg, M....

. 2020 ; 395 (10218) : 132-141. [pub] 20191210

Jazyk angličtina Země Velká Británie

Typ dokumentu klinické zkoušky, fáze III, časopisecké články, multicentrická studie, randomizované kontrolované studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc20005625
E-zdroje Online Plný text

NLK ProQuest Central od 1992-01-04 do Před 3 měsíci
Nursing & Allied Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Health & Medicine (ProQuest) od 1992-01-04 do Před 3 měsíci
Family Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Psychology Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Health Management Database (ProQuest) od 1992-01-04 do Před 3 měsíci
Public Health Database (ProQuest) od 1992-01-04 do Před 3 měsíci

Odkazy

PubMed 31836199
DOI 10.1016/s0140-6736(19)32956-3
Knihovny.cz E-zdroje

BACKGROUND: Standard-of-care treatment for patients with newly diagnosed multiple myeloma includes combination therapies for patients who are not eligible for autologous stem-cell transplantation. At the primary analysis for progression-free survival of the phase 3 ALCYONE trial, progression-free survival was significantly longer with daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) alone in patients with transplant-ineligible, newly diagnosed multiple myeloma. Here we report updated efficacy and safety results from a prespecified, interim, overall survival analysis of ALCYONE with more than 36 months of follow-up. METHODS: ALCYONE was a multicentre, randomised, open-label, active-controlled, phase 3 trial that enrolled patients between Feb 9, 2015, and July 14, 2016, at 162 sites in 25 countries across North America, South America, Europe, and the Asia-Pacific region. Patients were eligible for inclusion if they had newly diagnosed multiple myeloma and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation, because of their age (≥65 years) or because of substantial comorbidities. Patients were randomly assigned in a 1:1 ratio and by permuted block randomisation to receive D-VMP or VMP. An interactive web-based randomisation system was used. Randomisation was stratified by International Staging System disease stage, geographical region, and age. There was no masking to treatment assignments. All patients received up to nine 6-week cycles of subcutaneous bortezomib (1·3 mg/m2 of body surface area on days 1, 4, 8, 11, 22, 25, 29, and 32 of cycle one and on days 1, 8, 22, and 29 of cycles two through nine), oral melphalan (9 mg/m2 once daily on days 1 through 4 of each cycle), and oral prednisone (60 mg/m2 once daily on days 1 through 4 of each cycle). Patients in the D-VMP group also received intravenous daratumumab (16 mg/kg of bodyweight, once weekly during cycle one, once every 3 weeks in cycles two through nine, and once every 4 weeks thereafter as maintenance therapy until disease progression or unacceptable toxicity). The primary endpoint was progression-free survival, which has been reported previously. Results presented are from a prespecified interim analysis for overall survival. The primary analysis population (including for overall survival) was the intention-to-treat population of all patients who were randomly assigned to treatment. The safety population included patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02195479. FINDINGS: 706 patients were randomly assigned to treatment groups (350 to the D-VMP group, 356 to the VMP group). At a median follow-up of 40·1 months (IQR 37·4-43·1), a significant benefit in overall survival was observed for the D-VMP group. The hazard ratio (HR) for death in the D-VMP group compared with the VMP group was 0·60 (95% CI 0·46-0·80; p=0·0003). The Kaplan-Meier estimate of the 36-month rate of overall survival was 78·0% (95% CI 73·2-82·0) in the D-VMP group and 67·9% (62·6-72·6) in the VMP group. Progression-free survival, the primary endpoint, remained significantly improved for the D-VMP group (HR 0·42 [0·34-0·51]; p<0·0001). The most frequent adverse events during maintenance daratumumab monotherapy in patients in the D-VMP group were respiratory infections (54 [19%] of 278 patients had upper respiratory tract infections; 42 [15%] had bronchitis, 34 [12%] had viral upper respiratory tract infections), cough (34 [12%]), and diarrhoea (28 [10%]). INTERPRETATION: D-VMP prolonged overall survival in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. With more than 3 years of follow-up, the D-VMP group continued to show significant improvement in progression-free survival, with no new safety concerns. FUNDING: Janssen Research & Development.

1st Department of Medicine Semmelweis University Budapest Hungary

Andrew Love Cancer Centre Geelong Australia

Azienda Ospedaliera Santa Maria di Terni Terni Italy

Centro de Investigación Médica Aplicada Pamplona Spain

Champalimaud Centre for the Unknown Lisbon Portugal

CHU UCL Namur Université catholique de Louvain Yvoir Belgium

Clinic of Professional Pathology Saratov Russia

Clínica de tratamento e pesquisa em Hematologia e Oncologia Cuiaba Brazil

Department of Haematology Leicester Royal Infirmary Leicester UK

Department of Hematology and Cancer Prevention Chorzów School of Public Health Medical University of Silesia Katowice Poland

Department of Hematology Japanese Red Cross Medical Center Tokyo Japan

Department of Internal Medicine Seoul National University College of Medicine Seoul South Korea

Hospital Clínic de Barcelona Institut d'Investigacions Biomèdiques August Pi i Sunyer University of Barcelona Barcelona Spain

Instituto de Investigación Biomédica de Salamanca Hospital Universitario de Salamanca Salamanca Spain

Janssen Global Medical Affairs Horsham PA USA

Janssen Research and Development Raritan NJ USA

Janssen Research and Development Spring House PA USA

Matsuyama Red Cross Hospital Matsuyama Japan

Medinvent Institute of Health Tbilisi Georgia

National and Kapodistrian University of Athens Athens Greece

Seràgnoli Institute of Hematology Bologna University School of Medicine Bologna Italy

University Hospital Brno Brno Czech Republic

University Hospitals Birmingham NHS Trust Birmingham UK

University of Chicago Medical Center Chicago IL USA

Würzburg University Medical Center Würzburg Germany

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc20005625
003      
CZ-PrNML
005      
20200525100741.0
007      
ta
008      
200511s2020 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1016/S0140-6736(19)32956-3 $2 doi
035    __
$a (PubMed)31836199
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Mateos, Maria-Victoria $u Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Salamanca, Spain. Electronic address: mvmateos@usal.es.
245    10
$a Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial / $c MV. Mateos, M. Cavo, J. Blade, MA. Dimopoulos, K. Suzuki, A. Jakubowiak, S. Knop, C. Doyen, P. Lucio, Z. Nagy, L. Pour, M. Cook, S. Grosicki, A. Crepaldi, AM. Liberati, P. Campbell, T. Shelekhova, SS. Yoon, G. Iosava, T. Fujisaki, M. Garg, M. Krevvata, Y. Chen, J. Wang, A. Kudva, J. Ukropec, S. Wroblewski, M. Qi, R. Kobos, J. San-Miguel,
520    9_
$a BACKGROUND: Standard-of-care treatment for patients with newly diagnosed multiple myeloma includes combination therapies for patients who are not eligible for autologous stem-cell transplantation. At the primary analysis for progression-free survival of the phase 3 ALCYONE trial, progression-free survival was significantly longer with daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) alone in patients with transplant-ineligible, newly diagnosed multiple myeloma. Here we report updated efficacy and safety results from a prespecified, interim, overall survival analysis of ALCYONE with more than 36 months of follow-up. METHODS: ALCYONE was a multicentre, randomised, open-label, active-controlled, phase 3 trial that enrolled patients between Feb 9, 2015, and July 14, 2016, at 162 sites in 25 countries across North America, South America, Europe, and the Asia-Pacific region. Patients were eligible for inclusion if they had newly diagnosed multiple myeloma and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation, because of their age (≥65 years) or because of substantial comorbidities. Patients were randomly assigned in a 1:1 ratio and by permuted block randomisation to receive D-VMP or VMP. An interactive web-based randomisation system was used. Randomisation was stratified by International Staging System disease stage, geographical region, and age. There was no masking to treatment assignments. All patients received up to nine 6-week cycles of subcutaneous bortezomib (1·3 mg/m2 of body surface area on days 1, 4, 8, 11, 22, 25, 29, and 32 of cycle one and on days 1, 8, 22, and 29 of cycles two through nine), oral melphalan (9 mg/m2 once daily on days 1 through 4 of each cycle), and oral prednisone (60 mg/m2 once daily on days 1 through 4 of each cycle). Patients in the D-VMP group also received intravenous daratumumab (16 mg/kg of bodyweight, once weekly during cycle one, once every 3 weeks in cycles two through nine, and once every 4 weeks thereafter as maintenance therapy until disease progression or unacceptable toxicity). The primary endpoint was progression-free survival, which has been reported previously. Results presented are from a prespecified interim analysis for overall survival. The primary analysis population (including for overall survival) was the intention-to-treat population of all patients who were randomly assigned to treatment. The safety population included patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02195479. FINDINGS: 706 patients were randomly assigned to treatment groups (350 to the D-VMP group, 356 to the VMP group). At a median follow-up of 40·1 months (IQR 37·4-43·1), a significant benefit in overall survival was observed for the D-VMP group. The hazard ratio (HR) for death in the D-VMP group compared with the VMP group was 0·60 (95% CI 0·46-0·80; p=0·0003). The Kaplan-Meier estimate of the 36-month rate of overall survival was 78·0% (95% CI 73·2-82·0) in the D-VMP group and 67·9% (62·6-72·6) in the VMP group. Progression-free survival, the primary endpoint, remained significantly improved for the D-VMP group (HR 0·42 [0·34-0·51]; p<0·0001). The most frequent adverse events during maintenance daratumumab monotherapy in patients in the D-VMP group were respiratory infections (54 [19%] of 278 patients had upper respiratory tract infections; 42 [15%] had bronchitis, 34 [12%] had viral upper respiratory tract infections), cough (34 [12%]), and diarrhoea (28 [10%]). INTERPRETATION: D-VMP prolonged overall survival in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. With more than 3 years of follow-up, the D-VMP group continued to show significant improvement in progression-free survival, with no new safety concerns. FUNDING: Janssen Research & Development.
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a senioři nad 80 let $7 D000369
650    _2
$a monoklonální protilátky $x aplikace a dávkování $x škodlivé účinky $7 D000911
650    _2
$a bortezomib $x aplikace a dávkování $x škodlivé účinky $7 D000069286
650    _2
$a přežití bez známek nemoci $7 D018572
650    _2
$a rozvrh dávkování léků $7 D004334
650    _2
$a kombinovaná farmakoterapie $x škodlivé účinky $7 D004359
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé $7 D006801
650    _2
$a udržovací chemoterapie $7 D060046
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a melfalan $x aplikace a dávkování $x škodlivé účinky $7 D008558
650    _2
$a lidé středního věku $7 D008875
650    _2
$a mnohočetný myelom $x farmakoterapie $x mortalita $7 D009101
650    _2
$a prednison $x aplikace a dávkování $x škodlivé účinky $7 D011241
650    _2
$a analýza přežití $7 D016019
650    _2
$a výsledek terapie $7 D016896
651    _2
$a Asie $7 D001208
651    _2
$a Evropa $7 D005060
651    _2
$a Severní Amerika $7 D009656
651    _2
$a Jižní Amerika $7 D013020
655    _2
$a klinické zkoušky, fáze III $7 D017428
655    _2
$a časopisecké články $7 D016428
655    _2
$a multicentrická studie $7 D016448
655    _2
$a randomizované kontrolované studie $7 D016449
700    1_
$a Cavo, Michele $u Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy.
700    1_
$a Blade, Joan $u Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
700    1_
$a Dimopoulos, Meletios A $u National and Kapodistrian University of Athens, Athens, Greece.
700    1_
$a Suzuki, Kenshi $u Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.
700    1_
$a Jakubowiak, Andrzej $u University of Chicago Medical Center, Chicago, IL, USA.
700    1_
$a Knop, Stefan $u Würzburg University Medical Center, Würzburg, Germany.
700    1_
$a Doyen, Chantal $u CHU UCL Namur, Université catholique de Louvain, Yvoir, Belgium.
700    1_
$a Lucio, Paulo $u Champalimaud Centre for the Unknown, Lisbon, Portugal.
700    1_
$a Nagy, Zsolt $u 1st Department of Medicine, Semmelweis University, Budapest, Hungary.
700    1_
$a Pour, Ludek $u University Hospital Brno, Brno, Czech Republic.
700    1_
$a Cook, Mark $u University Hospitals Birmingham NHS Trust, Birmingham, UK.
700    1_
$a Grosicki, Sebastian $u Department of Hematology and Cancer Prevention, Chorzów School of Public Health, Medical University of Silesia, Katowice, Poland.
700    1_
$a Crepaldi, Andre $u Clínica de tratamento e pesquisa em Hematologia e Oncologia, Cuiaba, Brazil.
700    1_
$a Liberati, Anna Marina $u Azienda Ospedaliera Santa Maria di Terni, Terni, Italy.
700    1_
$a Campbell, Philip $u Andrew Love Cancer Centre, Geelong, Australia.
700    1_
$a Shelekhova, Tatiana $u Clinic of Professional Pathology, Saratov, Russia.
700    1_
$a Yoon, Sung-Soo $u Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
700    1_
$a Iosava, Genadi $u Medinvent Institute of Health, Tbilisi, Georgia.
700    1_
$a Fujisaki, Tomoaki $u Matsuyama Red Cross Hospital, Matsuyama, Japan.
700    1_
$a Garg, Mamta $u Department of Haematology, Leicester Royal Infirmary, Leicester, UK.
700    1_
$a Krevvata, Maria $u Janssen Research & Development, Spring House, PA, USA.
700    1_
$a Chen, Ying $u Janssen Research & Development, Raritan, NJ, USA.
700    1_
$a Wang, Jianping $u Janssen Research & Development, Raritan, NJ, USA.
700    1_
$a Kudva, Anupa $u Janssen Research & Development, Raritan, NJ, USA.
700    1_
$a Ukropec, Jon $u Janssen Global Medical Affairs, Horsham, PA, USA.
700    1_
$a Wroblewski, Susan $u Janssen Research & Development, Spring House, PA, USA.
700    1_
$a Qi, Ming $u Janssen Research & Development, Spring House, PA, USA.
700    1_
$a Kobos, Rachel $u Janssen Research & Development, Raritan, NJ, USA.
700    1_
$a San-Miguel, Jesus $u Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IDISNA), Centro de Investigación Biomédica en Red de Oncología (CIBERONC), Pamplona, Spain.
773    0_
$w MED00010161 $t Lancet (London, England) $x 1474-547X $g Roč. 395, č. 10218 (2020), s. 132-141
856    41
$u https://pubmed.ncbi.nlm.nih.gov/31836199 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20200511 $b ABA008
991    __
$a 20200525100741 $b ABA008
999    __
$a ok $b bmc $g 1524483 $s 1095681
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 395 $c 10218 $d 132-141 $e 20191210 $i 1474-547X $m Lancet $n Lancet $x MED00010161
LZP    __
$a Pubmed-20200511

Najít záznam

Citační ukazatele

Možnosti archivace