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Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial
MA. Dimopoulos, F. Gay, F. Schjesvold, M. Beksac, R. Hajek, KC. Weisel, H. Goldschmidt, V. Maisnar, P. Moreau, CK. Min, A. Pluta, WJ. Chng, M. Kaiser, S. Zweegman, MV. Mateos, A. Spencer, S. Iida, G. Morgan, K. Suryanarayan, Z. Teng, T. Skacel,...
Language English Country England, Great Britain
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 1992-01-04 to 3 months ago
Nursing & Allied Health Database (ProQuest)
from 1992-01-04 to 3 months ago
Health & Medicine (ProQuest)
from 1992-01-04 to 3 months ago
Family Health Database (ProQuest)
from 1992-01-04 to 3 months ago
Psychology Database (ProQuest)
from 1992-01-04 to 3 months ago
Health Management Database (ProQuest)
from 1992-01-04 to 3 months ago
Public Health Database (ProQuest)
from 1992-01-04 to 3 months ago
- MeSH
- Administration, Oral MeSH
- Transplantation, Autologous MeSH
- Time Factors MeSH
- Double-Blind Method MeSH
- Glycine administration & dosage adverse effects analogs & derivatives MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma drug therapy surgery MeSH
- Disease Progression MeSH
- Antineoplastic Agents administration & dosage adverse effects MeSH
- Boron Compounds administration & dosage adverse effects MeSH
- Stem Cell Transplantation * MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. METHODS: The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m2) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1-4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. FINDINGS: Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3-35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7-33·8] vs 21·3 months [18·0-24·7]; hazard ratio 0·72, 95% CI 0·58-0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group. INTERPRETATION: Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma. FUNDING: Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.
4th Department of Medicine Hematology FN and LF UK Hradec Králové Hradec Králové Czech Republic
Center for Hematology and Oncology University Hospital Zürich Zürich Switzerland
Department of Haematology The Royal Marsden Hospital London UK
Department of Hematology Ankara University Ankara Turkey
Department of Hematology University Hospital Hôtel Dieu University of Nantes Nantes France
Department of Hematology University Hospital of Salamanca CIC IBMCC Salamanca Spain
Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic
Department of Internal Medicine 2 University of Tuebingen Tuebingen Germany
Department of Internal Medicine Seoul St Mary's Hospital Seoul South Korea
Division of Hematology Department of Internal Medicine Mayo Clinic Rochester MN USA
Division of Molecular Pathology The Institute of Cancer Research ICR London UK
KG Jebsen Center for B cell malignancies University of Oslo Oslo Norway
Millennium Pharmaceuticals Cambridge MA USA
Myeloma Institute University of Arkansas for Medical Sciences Little Rock AR USA
References provided by Crossref.org
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- $a Dimopoulos, Meletios A $u Hematology & Medical Oncology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece. Electronic address: mdimop@med.uoa.gr.
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