TY - JOUR
T1 - Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma
AU - Kaiser, Martin
AU - Beksaç, Meral
AU - Gulbrandsen, Nina
AU - Schjesvold, Fredrik
AU - Hájek, Roman
AU - Moreau, Philippe
AU - de Arriba de la Fuente, Felipe
AU - Mateos, María Victoria
AU - West, Sharon
AU - Spencer, Andrew
AU - Rajkumar, S. Vincent
AU - Suryanarayan, Kaveri
AU - Czorniak, Michael
AU - Li, Cong
AU - Teng, Zhaoyang
AU - Labotka, Richard
AU - Dimopoulos, Meletios A.
N1 - Funding Information:
MK: consulting/advisory relationship with Abbvie, Amgen, BMS, Celgene, GSK, Janssen, Karyopharm, and Takeda; research funding from Celgene and Janssen; honoraria from Celgene, Janssen, Amgen, and Takeda
Funding Information:
The authors acknowledge Helen Wilkinson of FireKite, an Ashfield company, part of UDG Healthcare plc, for providing professional medical writing support, which was funded by Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and complied with Good Publication Practice-3 (GPP3) guidelines (Battisti WP et al. Ann Intern Med 2015; 163: 461?464). They would also like to thank Renda Ferrari, PhD (Millennium Pharmaceuticals, Inc.), for her contribution to the editorial and scientific content of the manuscript. TOURMALINE-MM3 was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding Information:
The authors acknowledge Helen Wilkinson of FireKite, an Ashfield company, part of UDG Healthcare plc, for providing professional medical writing support, which was funded by Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and complied with Good Publication Practice-3 (GPP3) guidelines (Battisti WP et al. Ann Intern Med 2015; 163: 461–464). They would also like to thank Renda Ferrari, PhD (Millennium Pharmaceuticals, Inc.), for her contribution to the editorial and scientific content of the manuscript. TOURMALINE-MM3 was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding Information:
This study was funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Acknowledgments
Funding Information:
FS: consulting/advisory relationship with Mundipharma, GSK, Pfizer/BMS, Novartis, Amgen, Celgene, Takeda, Bayer, Adaptive, Janssen, Oncopeptides, and MSD, Sanofi; research funding from Celgene, Mundipharma, Amgen, Novartis, Takeda, and Janssen; honoraria from Amgen, Mundipharma, Celgene, Teva, BMS, Takeda, Abbvie, Janssen, Novartis, and SkyliteDX; ownership interests with Oncopeptides
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - Adverse events
KW - Ixazomib
KW - Maintenance therapy
KW - Multiple myeloma
KW - Safety
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U2 - 10.1007/s00277-020-04149-5
DO - 10.1007/s00277-020-04149-5
M3 - Article
C2 - 32613281
AN - SCOPUS:85087309342
VL - 99
SP - 1793
EP - 1804
JO - Annals of Hematology
JF - Annals of Hematology
SN - 0939-5555
IS - 8
ER -