BACKGROUND: In the phase 3 ALCYONE study, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) significantly improved progression-free survival (PFS) and overall survival (OS) in transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. We present a subgroup analysis of ALCYONE by patient frailty status. PATIENTS AND METHODS: Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit (0), intermediate (1), or frail (≥2); a nonfrail category combined fit and intermediate patients. RESULTS: Among randomized patients (D-VMP, n = 350; VMP, n = 356), 391 (55.4%) were nonfrail (D-VMP, 187 [53.4%]; VMP, 204 [57.3%]) and 315 (44.6%) were frail (163 [46.6%]; 152 [42.7%]). After 40.1-months median follow-up, nonfrail patients had longer PFS and OS than frail patients, but benefits of D-VMP versus VMP were maintained across subgroups: PFS nonfrail (median, 45.7 vs. 19.1 months; hazard ratio [HR], 0.36; P < .0001), frail (32.9 vs. 19.5 months; HR, 0.51; P < .0001); OS nonfrail (36-month rate, 83.6% vs. 74.5%), frail (71.4% vs. 59.0%). Improved greater than or equal to complete response and minimal residual disease (10-5)-negativity rates were observed for D-VMP versus VMP across subgroups. The 2 most common grade 3/4 treatment-emergent adverse events were neutropenia (nonfrail: 39.2% [D-VMP] and 42.4% [VMP]; frail: 41.3% and 34.4%) and thrombocytopenia (nonfrail: 32.8% and 36.9%; frail: 36.9% and 39.1%). CONCLUSION: Our findings support the clinical benefit of D-VMP in transplant-ineligible NDMM patients enrolled in ALCYONE, regardless of frailty status.

Andrew Love Cancer Centre University Hospital Geelong Geelong VIC Australia

Champalimaud Centre for the Unknown Lisbon Portugal

Clinica de Tratamento E Cuiaba Brazil

Clínica Universidad de Navarra Centro de Investigación Médica Aplicada Pamplona Navarra Spain

Department of Hematology and Cancer Prevention in Chorzów Faculty of Health Sciences in Bytom Medical University of Silesia Katowice Poland

Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Mizuho cho Mizuho ku Nagoya 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

IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna Istituto di Ematologia Seràgnoli Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università degli Studi Bologna Italy

Janssen Global Medical Affairs Horsham PA

Janssen Research and Development Beerse Belgium

Janssen Research and Development LLC Raritan NJ

Janssen Research and Development LLC Spring House PA

Janssen Research and Development LLC Titusville NJ

Japanese Red Cross Medical Center Department of Hematology Tokyo Japan

Leicester Royal Infirmary Haematology Leicester United Kingdom

Matsuyama Red Cross Hospital Matsuyama Japan

Medinvest Institute of Hematology Tbilisi Georgia

National and Kapodistrian University of Athens Athens Greece

Semmelweis Egyetem Budapest Hungary

Università degli Studi di Perugia Azienda Ospedaliera Santa Maria Terni Italy

Université Catholique de Louvain Yvoir Belgium

University Hospital Brno Brno Bohunice Brno Starý Lískovec Czech Republic

University Hospital of Salamanca IBSAL Cancer Research Center IBMCC Salamanca Spain

Würzburg University Medical Center Würzburg Germany

000      

00000naa a2200000 a 4500

001      

bmc22011972

003      

CZ-PrNML

005      

20220506131004.0

007      

ta

008      

220425s2021 xxu f 000 0|eng||

009      

AR

024    7_

$a 10.1016/j.clml.2021.06.005 $2 doi

035    __

$a (PubMed)34344638

040    __

$a ABA008 $b cze $d ABA008 $e AACR2

041    0_

$a eng

044    __

$a xxu

100    1_

$a Mateos, Maria-Victoria $u University Hospital of Salamanca/IBSAL, Cancer Research Center IBMCC (USAL-CSIC), Salamanca, Spain. Electronic address: mvmateos@usal.es

245    10

$a Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE / $c MV. Mateos, MA. Dimopoulos, M. Cavo, K. Suzuki, S. Knop, C. Doyen, P. Lucio, Z. Nagy, L. Pour, S. Grosicki, A. Crepaldi, AM. Liberati, P. Campbell, SS. Yoon, G. Iosava, T. Fujisaki, M. Garg, S. Iida, J. Bladé, J. Ukropec, H. Pei, R. Van Rampelbergh, A. Kudva, M. Qi, J. San-Miguel

520    9_

$a BACKGROUND: In the phase 3 ALCYONE study, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) significantly improved progression-free survival (PFS) and overall survival (OS) in transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. We present a subgroup analysis of ALCYONE by patient frailty status. PATIENTS AND METHODS: Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit (0), intermediate (1), or frail (≥2); a nonfrail category combined fit and intermediate patients. RESULTS: Among randomized patients (D-VMP, n = 350; VMP, n = 356), 391 (55.4%) were nonfrail (D-VMP, 187 [53.4%]; VMP, 204 [57.3%]) and 315 (44.6%) were frail (163 [46.6%]; 152 [42.7%]). After 40.1-months median follow-up, nonfrail patients had longer PFS and OS than frail patients, but benefits of D-VMP versus VMP were maintained across subgroups: PFS nonfrail (median, 45.7 vs. 19.1 months; hazard ratio [HR], 0.36; P < .0001), frail (32.9 vs. 19.5 months; HR, 0.51; P < .0001); OS nonfrail (36-month rate, 83.6% vs. 74.5%), frail (71.4% vs. 59.0%). Improved greater than or equal to complete response and minimal residual disease (10-5)-negativity rates were observed for D-VMP versus VMP across subgroups. The 2 most common grade 3/4 treatment-emergent adverse events were neutropenia (nonfrail: 39.2% [D-VMP] and 42.4% [VMP]; frail: 41.3% and 34.4%) and thrombocytopenia (nonfrail: 32.8% and 36.9%; frail: 36.9% and 39.1%). CONCLUSION: Our findings support the clinical benefit of D-VMP in transplant-ineligible NDMM patients enrolled in ALCYONE, regardless of frailty status.

650    _2

$a senioři $7 D000368

650    _2

$a senioři nad 80 let $7 D000369

650    _2

$a monoklonální protilátky $x farmakologie $x terapeutické užití $7 D000911

650    _2

$a protokoly antitumorózní kombinované chemoterapie $x farmakologie $x terapeutické užití $7 D000971

650    _2

$a bortezomib $x farmakologie $x terapeutické užití $7 D000069286

650    _2

$a ženské pohlaví $7 D005260

650    _2

$a lidé $7 D006801

650    _2

$a mužské pohlaví $7 D008297

650    _2

$a melfalan $x farmakologie $x terapeutické užití $7 D008558

650    _2

$a mnohočetný myelom $x farmakoterapie $7 D009101

650    _2

$a prednison $x farmakologie $x terapeutické užití $7 D011241

655    _2

$a časopisecké články $7 D016428

655    _2

$a práce podpořená grantem $7 D013485

700    1_

$a Dimopoulos, Meletios A $u National and Kapodistrian University of Athens, Athens, Greece

700    1_

$a Cavo, Michele $u IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Istituto di Ematologia "Seràgnoli", Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi, Bologna, Italy

700    1_

$a Suzuki, Kenshi $u Japanese Red Cross Medical Center, Department of Hematology, Tokyo, Japan

700    1_

$a Knop, Stefan $u Würzburg University Medical Center, Würzburg, Germany

700    1_

$a Doyen, Chantal $u 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 Semmelweis Egyetem, Budapest, Hungary

700    1_

$a Pour, Ludek $u University Hospital Brno, Brno-Bohunice-Brno-Starý Lískovec, Czech Republic

700    1_

$a Grosicki, Sebastian $u Department of Hematology and Cancer Prevention in Chorzów, Faculty of Health Sciences in Bytom, Medical University of Silesia, Katowice, Poland

700    1_

$a Crepaldi, Andre $u Clinica de Tratamento E, Cuiaba, Brazil

700    1_

$a Liberati, Anna Marina $u Università degli Studi di Perugia Azienda Ospedaliera "Santa Maria," Terni, Italy

700    1_

$a Campbell, Philip $u Andrew Love Cancer Centre, University Hospital Geelong, Geelong, VIC, Australia

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 Medinvest-Institute of Hematology, Tbilisi, Georgia

700    1_

$a Fujisaki, Tomoaki $u Matsuyama Red Cross Hospital, Matsuyama, Japan

700    1_

$a Garg, Mamta $u Leicester Royal Infirmary - Haematology, Leicester, United Kingdom

700    1_

$a Iida, Shinsuke $u Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku Nagoya, Japan

700    1_

$a Bladé, Joan $u Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

700    1_

$a Ukropec, Jon $u Janssen Global Medical Affairs, Horsham, PA

700    1_

$a Pei, Huiling $u Janssen Research & Development, LLC, Titusville, NJ

700    1_

$a Van Rampelbergh, Rian $u Janssen Research & Development, Beerse, Belgium

700    1_

$a Kudva, Anupa $u Janssen Research & Development, LLC, Raritan, NJ

700    1_

$a Qi, Ming $u Janssen Research & Development, LLC, Spring House, PA

700    1_

$a San-Miguel, Jesus $u Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarra, Spain

773    0_

$w MED00180199 $t Clinical lymphoma, myeloma & leukemia $x 2152-2669 $g Roč. 21, č. 11 (2021), s. 785-798

856    41

$u https://pubmed.ncbi.nlm.nih.gov/34344638 $y Pubmed

910    __

$a ABA008 $b sig $c sign $y p $z 0

990    __

$a 20220425 $b ABA008

991    __

$a 20220506130957 $b ABA008

999    __

$a ok $b bmc $g 1789519 $s 1163173

BAS    __

$a 3

BAS    __

$a PreBMC

BMC    __

$a 2021 $b 21 $c 11 $d 785-798 $e 20210618 $i 2152-2669 $m Clinical lymphoma, myeloma & leukemia $n Clin Lymphoma Myeloma Leuk $x MED00180199

LZP    __

$a Pubmed-20220425