Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma.
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Date
2020-08-01ICR Author
Author
Kaiser, M
Beksaç, M
Gulbrandsen, N
Schjesvold, F
Hájek, R
Moreau, P
de Arriba de la Fuente, F
Mateos, M-V
West, S
Spencer, A
Rajkumar, SV
Suryanarayan, K
Czorniak, M
Li, C
Teng, Z
Labotka, R
Dimopoulos, MA
Type
Journal Article
Metadata
Show full item recordAbstract
The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1-4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413.
Collections
Subject
Humans
Multiple Myeloma
Boron Compounds
Silicates
Glycine
Antineoplastic Combined Chemotherapy Protocols
Disease-Free Survival
Stem Cell Transplantation
Survival Rate
Follow-Up Studies
Aged
Middle Aged
Female
Male
Autografts
Research team
Myeloma Group
Language
eng
Date accepted
2020-06-14
License start date
2020-08
Citation
Annals of hematology, 2020, 99 (8), pp. 1793 - 1804
Publisher
SPRINGER