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


Journal

Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386

Informations de publication

Date de publication:
11 2021
Historique:
received: 21 05 2021
accepted: 02 06 2021
pubmed: 5 8 2021
medline: 17 2 2022
entrez: 4 8 2021
Statut: ppublish

Résumé

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. 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. 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 Our findings support the clinical benefit of D-VMP in transplant-ineligible NDMM patients enrolled in ALCYONE, regardless of frailty status.

Sections du résumé

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
CONCLUSION
Our findings support the clinical benefit of D-VMP in transplant-ineligible NDMM patients enrolled in ALCYONE, regardless of frailty status.

Identifiants

pubmed: 34344638
pii: S2152-2650(21)00210-X
doi: 10.1016/j.clml.2021.06.005
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
daratumumab 4Z63YK6E0E
Bortezomib 69G8BD63PP
Melphalan Q41OR9510P
Prednisone VB0R961HZT

Banques de données

ClinicalTrials.gov
['NCT02195479']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

785-798

Informations de copyright

Copyright © 2021 Janssen Research & Development, LLC. Published by Elsevier Inc. All rights reserved.

Auteurs

Maria-Victoria Mateos (MV)

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

Meletios A Dimopoulos (MA)

National and Kapodistrian University of Athens, Athens, Greece.

Michele Cavo (M)

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

Kenshi Suzuki (K)

Japanese Red Cross Medical Center, Department of Hematology, Tokyo, Japan.

Stefan Knop (S)

Würzburg University Medical Center, Würzburg, Germany.

Chantal Doyen (C)

Université Catholique de Louvain, Yvoir, Belgium.

Paulo Lucio (P)

Champalimaud Centre for the Unknown, Lisbon, Portugal.

Zsolt Nagy (Z)

Semmelweis Egyetem, Budapest, Hungary.

Ludek Pour (L)

University Hospital Brno, Brno-Bohunice-Brno-Starý Lískovec, Czech Republic.

Sebastian Grosicki (S)

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

Andre Crepaldi (A)

Clinica de Tratamento E, Cuiaba, Brazil.

Anna Marina Liberati (AM)

Università degli Studi di Perugia Azienda Ospedaliera "Santa Maria," Terni, Italy.

Philip Campbell (P)

Andrew Love Cancer Centre, University Hospital Geelong, Geelong, VIC, Australia.

Sung-Soo Yoon (SS)

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

Genadi Iosava (G)

Medinvest-Institute of Hematology, Tbilisi, Georgia.

Tomoaki Fujisaki (T)

Matsuyama Red Cross Hospital, Matsuyama, Japan.

Mamta Garg (M)

Leicester Royal Infirmary - Haematology, Leicester, United Kingdom.

Shinsuke Iida (S)

Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku Nagoya, Japan.

Joan Bladé (J)

Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Jon Ukropec (J)

Janssen Global Medical Affairs, Horsham, PA.

Huiling Pei (H)

Janssen Research & Development, LLC, Titusville, NJ.

Rian Van Rampelbergh (R)

Janssen Research & Development, Beerse, Belgium.

Anupa Kudva (A)

Janssen Research & Development, LLC, Raritan, NJ.

Ming Qi (M)

Janssen Research & Development, LLC, Spring House, PA.

Jesus San-Miguel (J)

Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Navarra, Spain.

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