All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma.
Administration, Oral
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Australia
Boron Compounds
/ administration & dosage
Contraindications, Procedure
Cyclophosphamide
/ administration & dosage
Dexamethasone
/ administration & dosage
Disease Progression
Eligibility Determination
Europe
Female
Glycine
/ administration & dosage
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Male
Middle Aged
Multiple Myeloma
/ diagnosis
Progression-Free Survival
Time Factors
United States
Elderly
Multiple myeloma
Newly diagnosed
Oral therapy
Transplant-ineligible
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:
01 2019
01 2019
Historique:
received:
27
06
2018
revised:
07
09
2018
accepted:
15
09
2018
pubmed:
25
11
2018
medline:
6
5
2020
entrez:
25
11
2018
Statut:
ppublish
Résumé
Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61-87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1-29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related). ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. NCT02046070.
Sections du résumé
BACKGROUND
Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance.
PATIENTS AND METHODS
Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m
RESULTS
Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61-87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1-29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related).
CONCLUSIONS
ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients.
TRIAL REGISTRATION NUMBER
NCT02046070.
Identifiants
pubmed: 30471652
pii: S0959-8049(18)31381-9
doi: 10.1016/j.ejca.2018.09.011
pii:
doi:
Substances chimiques
Boron Compounds
0
ixazomib
71050168A2
Dexamethasone
7S5I7G3JQL
Cyclophosphamide
8N3DW7272P
Glycine
TE7660XO1C
Banques de données
ClinicalTrials.gov
['NCT02046070']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-98Informations de copyright
Copyright © 2018. Published by Elsevier Ltd.