Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: A randomized, open-label study.
Dexamethasone
Drug therapy
Followup study
Lenalidomide
Smoldering multiple myeloma
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
29
05
2022
revised:
23
07
2022
accepted:
26
07
2022
pubmed:
7
9
2022
medline:
21
9
2022
entrez:
6
9
2022
Statut:
ppublish
Résumé
Smoldering multiple myeloma (SMM) is a heterogeneous disease in terms of progression to myeloma (MM), but its standard of care continues to be observation. The QuiRedex phase 3 trial initiated in 2007 included 119 high-risk patients with SMM randomized to treatment or observation. Treatment consisted of nine 4-week induction cycles (lenalidomide [Rd], 25 mg on days 1-21 plus dexamethasone, 20 mg on days 1-4 and 12-15), followed by maintenance (R, 10 mg on days 1-21) for up to 2 years. The primary end-point was time to progression (TTP) to myeloma based on per protocol population. Secondary end-points were overall survival (OS), response rate, and safety. An update of the trial after a long-term follow-up is presented here. This trial was registered with ClinicalTrials.gov (NCT00480363). After a median follow-up time of 12.5 years (range: 10.4-13.6), the median TTP to MM was 2.1 years in the observation arm and 9.5 years in the Rd arm (HR: 0.28, 95% CI: 0.18-0.44, p < 0.0001). The median OS was 8.5 years in the abstention arm and not reached in the Rd group (HR: 0.57, 95% CI: 0.34-0.95, p = 0.032). Patients who progressed received optimized treatments according to the standards of care, and the OS from progression was comparable in both arms (p = 0.96). This analysis confirms that early treatment with Rd for high-risk SMM translates into a sustained benefit in both TTP and OS. Pethema (Spanish Program for the Treatment of Hematologic Diseases), Spain.
Sections du résumé
BACKGROUND
Smoldering multiple myeloma (SMM) is a heterogeneous disease in terms of progression to myeloma (MM), but its standard of care continues to be observation.
METHODS
The QuiRedex phase 3 trial initiated in 2007 included 119 high-risk patients with SMM randomized to treatment or observation. Treatment consisted of nine 4-week induction cycles (lenalidomide [Rd], 25 mg on days 1-21 plus dexamethasone, 20 mg on days 1-4 and 12-15), followed by maintenance (R, 10 mg on days 1-21) for up to 2 years. The primary end-point was time to progression (TTP) to myeloma based on per protocol population. Secondary end-points were overall survival (OS), response rate, and safety. An update of the trial after a long-term follow-up is presented here. This trial was registered with ClinicalTrials.gov (NCT00480363).
FINDINGS
After a median follow-up time of 12.5 years (range: 10.4-13.6), the median TTP to MM was 2.1 years in the observation arm and 9.5 years in the Rd arm (HR: 0.28, 95% CI: 0.18-0.44, p < 0.0001). The median OS was 8.5 years in the abstention arm and not reached in the Rd group (HR: 0.57, 95% CI: 0.34-0.95, p = 0.032). Patients who progressed received optimized treatments according to the standards of care, and the OS from progression was comparable in both arms (p = 0.96).
INTERPRETATION
This analysis confirms that early treatment with Rd for high-risk SMM translates into a sustained benefit in both TTP and OS.
FUNDING
Pethema (Spanish Program for the Treatment of Hematologic Diseases), Spain.
Identifiants
pubmed: 36067617
pii: S0959-8049(22)00464-6
doi: 10.1016/j.ejca.2022.07.030
pii:
doi:
Substances chimiques
Dexamethasone
7S5I7G3JQL
Lenalidomide
F0P408N6V4
Banques de données
ClinicalTrials.gov
['NCT00480363']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
243-250Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.