Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Boron Compounds
/ administration & dosage
Dexamethasone
/ administration & dosage
Female
Glycine
/ administration & dosage
Humans
Induction Chemotherapy
Maintenance Chemotherapy
Male
Middle Aged
Multiple Myeloma
/ drug therapy
Progression-Free Survival
Survival Rate
Thalidomide
/ administration & dosage
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
03
05
2019
accepted:
27
08
2019
revised:
11
08
2019
pubmed:
29
9
2019
medline:
17
6
2020
entrez:
28
9
2019
Statut:
ppublish
Résumé
Ixazomib-revlimid-dexamethason showed significant activity in relapsed/refractory multiple myeloma (RRMM). Here, we evaluate ixazomib in combination with thalidomide and dexamethasone for induction treatment followed by ixazomib maintenance therapy in RRMM patients. Ninety patients have been included. Ixazomib-thalidomide-dexamethasone (4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly) was scheduled for eight cycles followed by maintenance with ixazomib for one year. The overall response rate was 51.1%, 23.3% achieved CR or VGPR and 10% MR resulting in a clinical benefit rate of 61.1%. In patients completing ≥2 cycles, the rates were 60.5%, 27.6% and 68.4%, respectively. Median progression-free survival (PFS) was 8.5 months in all, and 9.4 months in those completing ≥2 cycles. Response rates, PFS and overall survival (OS) were similar in patients with and without t(4;14) and/or del(17p), but PFS and OS was significantly shorter in patients with gain of 1q21. Multivariate regression analysis revealed gain of 1q21 as the most important factor associated with OS. Ixazomib maintenance resulted in an upgrade in the depth of response in 12.4% of patients. Grade 3/4 toxicities were relatively rare. Ixazomib-thalidomide-dexamethasone followed by ixazomib maintenance therapy is active and well tolerated in patients with RRMM. NCT02410694.
Sections du résumé
BACKGROUND
Ixazomib-revlimid-dexamethason showed significant activity in relapsed/refractory multiple myeloma (RRMM). Here, we evaluate ixazomib in combination with thalidomide and dexamethasone for induction treatment followed by ixazomib maintenance therapy in RRMM patients.
METHODS
Ninety patients have been included. Ixazomib-thalidomide-dexamethasone (4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly) was scheduled for eight cycles followed by maintenance with ixazomib for one year.
RESULTS
The overall response rate was 51.1%, 23.3% achieved CR or VGPR and 10% MR resulting in a clinical benefit rate of 61.1%. In patients completing ≥2 cycles, the rates were 60.5%, 27.6% and 68.4%, respectively. Median progression-free survival (PFS) was 8.5 months in all, and 9.4 months in those completing ≥2 cycles. Response rates, PFS and overall survival (OS) were similar in patients with and without t(4;14) and/or del(17p), but PFS and OS was significantly shorter in patients with gain of 1q21. Multivariate regression analysis revealed gain of 1q21 as the most important factor associated with OS. Ixazomib maintenance resulted in an upgrade in the depth of response in 12.4% of patients. Grade 3/4 toxicities were relatively rare.
CONCLUSIONS
Ixazomib-thalidomide-dexamethasone followed by ixazomib maintenance therapy is active and well tolerated in patients with RRMM.
TRIAL REGISTRATION NUMBER
NCT02410694.
Identifiants
pubmed: 31558804
doi: 10.1038/s41416-019-0581-8
pii: 10.1038/s41416-019-0581-8
pmc: PMC6889132
doi:
Substances chimiques
Boron Compounds
0
Thalidomide
4Z8R6ORS6L
ixazomib
71050168A2
Dexamethasone
7S5I7G3JQL
Glycine
TE7660XO1C
Banques de données
ClinicalTrials.gov
['NCT02410694']
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
751-757Références
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