Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk.
Abnormal Karyotype
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Bortezomib
/ administration & dosage
Dexamethasone
/ administration & dosage
Female
Follow-Up Studies
Humans
In Situ Hybridization, Fluorescence
Kaplan-Meier Estimate
Male
Middle Aged
Multiple Myeloma
/ drug therapy
Neoplasm, Residual
Progression-Free Survival
Recurrence
Risk
Clinical trials
Multiple myeloma
Myeloma therapy
Journal
Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937
Informations de publication
Date de publication:
20 08 2020
20 08 2020
Historique:
received:
08
04
2020
accepted:
30
07
2020
entrez:
22
8
2020
pubmed:
21
8
2020
medline:
7
4
2021
Statut:
epublish
Résumé
Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM). This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10 After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR. These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status. ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014.
Sections du résumé
BACKGROUND
Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM).
METHODS
This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10
RESULTS
After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR.
CONCLUSION
These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014.
Identifiants
pubmed: 32819447
doi: 10.1186/s13045-020-00948-5
pii: 10.1186/s13045-020-00948-5
pmc: PMC7439722
doi:
Substances chimiques
Antibodies, Monoclonal
0
daratumumab
4Z63YK6E0E
Bortezomib
69G8BD63PP
Dexamethasone
7S5I7G3JQL
Banques de données
ClinicalTrials.gov
['NCT02136134']
Types de publication
Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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