Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
Language English Country United States Media print
Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
27119237
DOI
10.1056/nejmoa1516282
Knihovny.cz E-resources
- MeSH
- Administration, Oral MeSH
- Dexamethasone administration & dosage MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Exanthema chemically induced MeSH
- Glycine administration & dosage adverse effects analogs & derivatives MeSH
- Kaplan-Meier Estimate MeSH
- Quality of Life MeSH
- Lenalidomide MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma drug therapy MeSH
- Disease-Free Survival MeSH
- Proportional Hazards Models MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Boron Compounds administration & dosage adverse effects MeSH
- Thalidomide administration & dosage analogs & derivatives MeSH
- Thrombocytopenia chemically induced MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged 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
- Comparative Study MeSH
- Names of Substances
- Dexamethasone MeSH
- Glycine MeSH
- ixazomib MeSH Browser
- Lenalidomide MeSH
- Boron Compounds MeSH
- Thalidomide MeSH
BACKGROUND: Ixazomib is an oral proteasome inhibitor that is currently being studied for the treatment of multiple myeloma. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma to receive ixazomib plus lenalidomide-dexamethasone (ixazomib group) or placebo plus lenalidomide-dexamethasone (placebo group). The primary end point was progression-free survival. RESULTS: Progression-free survival was significantly longer in the ixazomib group than in the placebo group at a median follow-up of 14.7 months (median progression-free survival, 20.6 months vs. 14.7 months; hazard ratio for disease progression or death in the ixazomib group, 0.74; P=0.01); a benefit with respect to progression-free survival was observed with the ixazomib regimen, as compared with the placebo regimen, in all prespecified patient subgroups, including in patients with high-risk cytogenetic abnormalities. The overall rates of response were 78% in the ixazomib group and 72% in the placebo group, and the corresponding rates of complete response plus very good partial response were 48% and 39%. The median time to response was 1.1 months in the ixazomib group and 1.9 months in the placebo group, and the corresponding median duration of response was 20.5 months and 15.0 months. At a median follow-up of approximately 23 months, the median overall survival has not been reached in either study group, and follow-up is ongoing. The rates of serious adverse events were similar in the two study groups (47% in the ixazomib group and 49% in the placebo group), as were the rates of death during the study period (4% and 6%, respectively); adverse events of at least grade 3 severity occurred in 74% and 69% of the patients, respectively. Thrombocytopenia of grade 3 and grade 4 severity occurred more frequently in the ixazomib group (12% and 7% of the patients, respectively) than in the placebo group (5% and 4% of the patients, respectively). Rash occurred more frequently in the ixazomib group than in the placebo group (36% vs. 23% of the patients), as did gastrointestinal adverse events, which were predominantly low grade. The incidence of peripheral neuropathy was 27% in the ixazomib group and 22% in the placebo group (grade 3 events occurred in 2% of the patients in each study group). Patient-reported quality of life was similar in the two study groups. CONCLUSIONS: The addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited. (Funded by Millennium Pharmaceuticals; TOURMALINE-MM1 ClinicalTrials.gov number, NCT01564537.).
References provided by Crossref.org
More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia-Like Multiple Myeloma
Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up
Development and validation of a novel risk stratification algorithm for relapsed multiple myeloma
Insights on Multiple Myeloma Treatment Strategies
Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma
Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting
ClinicalTrials.gov
NCT01564537