Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma
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Published:2020-07-01
Issue:8
Volume:99
Page:1793-1804
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ISSN:0939-5555
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Container-title:Annals of Hematology
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language:en
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Short-container-title:Ann Hematol
Author:
Kaiser Martin,Beksaç Meral,Gulbrandsen Nina,Schjesvold Fredrik,Hájek Roman,Moreau Philippe,de Arriba de la Fuente Felipe,Mateos María-Victoria,West Sharon,Spencer Andrew,Rajkumar S. Vincent,Suryanarayan Kaveri,Czorniak Michael,Li Cong,Teng Zhaoyang,Labotka Richard,Dimopoulos Meletios A.
Abstract
AbstractThe 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
Funder
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
Publisher
Springer Science and Business Media LLC
Subject
Hematology,General Medicine
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