Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE

被引：42

作者：

Mateos, Maria-Victoria ^{[1
]}

Dimopoulos, Meletios A. ^{[2
]}

Cavo, Michele ^{[3
]}

Suzuki, Kenshi ^{[4
]}

Knop, Stefan ^{[5
]}

Doyen, Chantal ^{[6
]}

Lucio, Paulo ^{[7
]}

Nagy, Zsolt ^{[8
]}

Pour, Ludek ^{[9
]}

Grosicki, Sebastian ^{[10
]}

Crepaldi, Andre ^{[11
]}

Liberati, Anna Marina ^{[12
]}

Campbell, Philip ^{[13
]}

Yoon, Sung-Soo ^{[14
]}

Iosava, Genadi ^{[15
]}

Fujisaki, Tomoaki ^{[16
]}

Garg, Mamta ^{[17
]}

Iida, Shinsuke ^{[18
]}

Blade, Joan ^{[19
]}

Ukropec, Jon ^{[20
]}

Pei, Huiling ^{[21
]}

Van Rampelbergh, Rian ^{[22
]}

Kudva, Anupa ^{[23
]}

Qi, Ming ^{[24
]}

San-Miguel, Jesus ^{[25
]}

机构：

[1] Univ Hosp Salamanca IBSAL, Canc Res Ctr IBMCC USAL CSIC, Paseo San Vicente 58-182, Salamanca 37007, Spain

[2] Natl & Kapodistrian Univ Athens, Athens, Greece

[3] Univ Bologna, IRCCS Azienda Osped Univ Bologna, Dipartimento Med Specialist Diagnost & Sperimenta, Ist Ematol Seragnoli, Bologna, Italy

[4] Japanese Red Cross Med Ctr, Dept Hematol, Tokyo, Japan

[5] Wurzburg Univ, Med Ctr, Wurzburg, Germany

[6] Catholic Univ Louvain, Yvoir, Belgium

[7] Champalimaud Ctr Unknown, Lisbon, Portugal

[8] Semmelweis Egyet, Budapest, Hungary

[9] Univ Hosp Brno, Brno Bohunice Brno Stary, Czech Republic

[10] Med Univ Silesia, Fac Hlth Sci Bytom, Dept Hematol & Canc Prevent Chorzow, Katowice, Poland

[11] Clin Tratamento E, Cuiaba, Brazil

[12] Univ Perugia, Azienda Osped Santa Maria, Terni, Italy

[13] Univ Hosp Geelong, Andrew Love Canc Ctr, Geelong, Vic, Australia

[14] Seoul Natl Univ, Dept Internal Med, Coll Med, Seoul, South Korea

[15] Medinvest Inst Hematol, Tbilisi, Georgia

[16] Matsuyama Red Cross Hosp, Matsuyama, Ehime, Japan

[17] Leicester Royal Infirm Haematol, Leicester, Leics, England

[18] Nagoya City Univ, Dept Hematol & Oncol, Grad Sch Med Sci, Mizuho Ku, Mizuho Cho, Nagoya, Aichi, Japan

[19] Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Barcelona, Spain

[20] Janssen Global Med Affairs, Horsham, PA USA

[21] Janssen Res & Dev LLC, Titusville, NJ USA

[22] Janssen Res & Dev, Beerse, Belgium

[23] Janssen Res & Dev LLC, Raritan, NJ USA

[24] Janssen Res & Dev LLC, Spring House, PA USA

[25] Clin Univ Navarra, Ctr Invest Med Aplicada CIMA, Inst Invest Sanitaria Navarra IDISNA, Navarra, Spain

来源：

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA | 2021年 / 21卷 / 11期

关键词：

CD38; Clinical study; Efficacy; Frail; Monoclonal antibody; ANTIBODY DARATUMUMAB; OPEN-LABEL; DEXAMETHASONE; SURVIVAL; LENALIDOMIDE; MONOTHERAPY; CD38;

D O I：

10.1016/j.clml.2021.06.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In the global phase 3 ALCYONE study, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) significantly improved outcomes versus VMP in transplant-ineligible patients with newly diagnosed multiple myeloma. In this subgroup analysis of ALCYONE, frailty was assessed retrospectively among all randomized patients (D-VMP, n = 350; VMP, n = 356). Improved efficacy with D-VMP versus VMP was observed across frailty subgroups, with no new safety concerns. 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 followup, 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.

引用

页码：785 / 798

页数：14

共 26 条

[1] High-Parameter Mass Cytometry Evaluation of Relapsed/Refractory Multiple Myeloma Patients Treated with Daratumumab Demonstrates Immune Modulation as a Novel Mechanism of Action [J].

Adams, Homer C., III ;

Stevenaert, Frederik ;

Krejcik, Jakub ;

Van der Borght, Koen ;

Smets, Tina ;

Bald, Jaime ;

Abraham, Yann ;

Ceulemans, Hugo ;

Chiu, Christopher ;

Vanhoof, Greet ;

Usmani, Saad Z. ;

Plesner, Torben ;

Lonial, Sagar ;

Nijhof, Inger ;

Lokhorst, Henk M. ;

Mutis, Tuna ;

van de Donk, Niels W. C. J. ;

Sasser, Amy Kate ;

Casneuf, Tineke .

CYTOMETRY PART A, 2019, 95A (03) :279-289

[2] Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials [J].

Bringhen, Sara ;

Victoria Mateos, Maria ;

Zweegman, Sonja ;

Larocca, Alessandra ;

Falcone, Antonietta Pia ;

Oriol, Albert ;

Rossi, Davide ;

Cavalli, Maide ;

Wijermans, Pierre ;

Ria, Roberto ;

Offidani, Massimo ;

Jose Lahuerta, Juan ;

Liberati, Anna Marina ;

Mina, Roberto ;

Callea, Vincenzo ;

Schaafsma, Martijn ;

Cerrato, Chiara ;

Marasca, Roberto ;

Franceschini, Luca ;

Evangelista, Andrea ;

Teruel, Ana-Isabel ;

van der Holt, Bronno ;

Montefusco, Vittorio ;

Ciccone, Giovannino ;

Boccadoro, Mario ;

San Miguel, Jesus ;

Sonneveld, Pieter ;

Palumbo, Antonio .

HAEMATOLOGICA, 2013, 98 (06) :980-987

[3] Efficacy and safety of once-weekly bortezomib in multiple myeloma patients [J].

Bringhen, Sara ;

Larocca, Alessandra ;

Rossi, Davide ;

Cavalli, Maide ;

Genuardi, Mariella ;

Ria, Roberto ;

Gentili, Silvia ;

Patriarca, Francesca ;

Nozzoli, Chiara ;

Levi, Anna ;

Guglielmelli, Tommasina ;

Benevolo, Giulia ;

Callea, Vincenzo ;

Rizzo, Vincenzo ;

Cangialosi, Clotilde ;

Musto, Pellegrino ;

De Rosa, Luca ;

Liberati, Anna Marina ;

Grasso, Mariella ;

Falcone, Antonietta P. ;

Evangelista, Andrea ;

Cavo, Michele ;

Gaidano, Gianluca ;

Boccadoro, Mario ;

Palumbo, Antonio .

BLOOD, 2010, 116 (23) :4745-4753

[4] Deep immune profiling of patients treated with lenalidomide and dexamethasone with or without daratumumab [J].

Casneuf, Tineke ;

Adams, Homer C., III ;

van de Donk, Niels W. C. J. ;

Abraham, Yann ;

Bald, Jaime ;

Vanhoof, Greet ;

Van der Borght, Koen ;

Smets, Tina ;

Foulk, Brad ;

Nielsen, Karl C. ;

Rusbuldt, Joshua ;

Axel, Amy ;

Lysaght, Andrew ;

Ceulemans, Hugo ;

Stevenaert, Frederik ;

Usmani, Saad Z. ;

Plesner, Torben ;

Avet-Loiseau, Herve ;

Nijhof, Inger ;

Mutis, Tuna ;

Schecter, Jordan M. ;

Chiu, Christopher ;

Bahlis, Nizar J. .

LEUKEMIA, 2021, 35 (02) :573-584

[5]

CAVO M, 2018, J CLIN ONCOL S, V36

[6] Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma [J].

Chari, Ajai ;

Suvannasankha, Attaya ;

Fay, Joseph W. ;

Arnulf, Bertrand ;

Kaufman, Jonathan L. ;

Ifthikharuddin, Jainulabdeen J. ;

Weiss, Brendan M. ;

Krishnan, Amrita ;

Lentzsch, Suzanne ;

Comenzo, Raymond ;

Wang, Jianping ;

Nottage, Kerri ;

Chiu, Christopher ;

Khokhar, Nushmia Z. ;

Ahmadi, Tahamtan ;

Lonial, Sagar .

BLOOD, 2017, 130 (08) :974-981

[7] Defining the vulnerable patient with myeloma-a frailty position paper of the European Myeloma Network [J].

Cook, Gordon ;

Larocca, Alessandra ;

Facon, Thierry ;

Zweegman, Sonja ;

Engelhardt, Monika .

LEUKEMIA, 2020, 34 (09) :2285-2294

[8] Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors [J].

de Weers, Michel ;

Tai, Yu-Tzu ;

van der Veer, Michael S. ;

Bakker, Joost M. ;

Vink, Tom ;

Jacobs, Danielle C. H. ;

Oomen, Lukas A. ;

Peipp, Matthias ;

Valerius, Thomas ;

Slootstra, Jerry W. ;

Mutis, Tuna ;

Bleeker, Wim K. ;

Anderson, Kenneth C. ;

Lokhorst, Henk M. ;

van de Winkel, Jan G. J. ;

Parren, Paul W. H. I. .

JOURNAL OF IMMUNOLOGY, 2011, 186 (03) :1840-1848

[9] Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma [J].

Dimopoulos, M. A. ;

Oriol, A. ;

Nahi, H. ;

San-Miguel, J. ;

Bahlis, N. J. ;

Usmani, S. Z. ;

Rabin, N. ;

Orlowski, R. Z. ;

Komarnicki, M. ;

Suzuki, K. ;

Plesner, T. ;

Yoon, S. -S. ;

Ben Yehuda, D. ;

Richardson, P. G. ;

Goldschmidt, H. ;

Reece, D. ;

Lisby, S. ;

Khokhar, N. Z. ;

O'Rourke, L. ;

Chiu, C. ;

Qin, X. ;

Guckert, M. ;

Ahmadi, T. ;

Moreau, P. .

NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (14) :1319-1331

[10]

European Medicines Agency, 2020, DARZALEX 20 MG ML CO

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