Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Language English Country United States Media print-electronic
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
34111952
DOI
10.1200/jco.21.00972
Knihovny.cz E-resources
- MeSH
- Survival Analysis MeSH
- Dexamethasone administration & dosage adverse effects MeSH
- Double-Blind Method MeSH
- Glycine administration & dosage adverse effects analogs & derivatives MeSH
- Quality of Life MeSH
- Lenalidomide administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma drug therapy mortality pathology MeSH
- Follow-Up Studies MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Aged MeSH
- Boron Compounds administration & dosage adverse effects MeSH
- Neoplasm Staging MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged 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
- Names of Substances
- Dexamethasone MeSH
- Glycine MeSH
- ixazomib MeSH Browser
- Lenalidomide MeSH
- Boron Compounds MeSH
PURPOSE: The double-blind, placebo-controlled, phase III TOURMALINE-MM1 study demonstrated a statistically significant improvement in progression-free survival with ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd in patients with relapsed or refractory multiple myeloma. We report the final analyses for overall survival (OS). PATIENTS AND METHODS: Patients were randomly assigned to ixazomib-Rd (n = 360) or placebo-Rd (n = 362), stratified by number of prior therapies (1 v 2 or 3), previous proteasome inhibitor (PI) exposure (yes v no), and International Staging System disease stage (I or II v III). OS (intent-to-treat population) was a key secondary end point. RESULTS: With a median follow-up of 85 months, median OS with ixazomib-Rd versus placebo-Rd was 53.6 versus 51.6 months (hazard ratio, 0.939; P = .495). Lower hazard ratios, indicating larger magnitude of OS benefit with ixazomib-Rd versus placebo-Rd, were seen in predefined subgroups: refractory to any (0.794) or last (0.742) treatment line; age > 65-75 years (0.757); International Staging System stage III (0.779); 2/3 prior therapies (0.845); high-risk cytogenetics (0.870); and high-risk cytogenetics and/or 1q21 amplification (0.862). Following ixazomib-Rd versus placebo-Rd, 71.7% versus 69.9% of patients received ≥ 1 anticancer therapy, of whom 24.7% versus 33.9% received daratumumab and 71.8% versus 76.9% received PIs (next-line therapy: 47.5% v 55.8%). Rates of new primary malignancies were similar with ixazomib-Rd (10.3%) and placebo-Rd (11.9%). There were no new or additional safety concerns. CONCLUSION: Median OS values in both arms were the longest reported in phase III studies of Rd-based triplets in relapsed or refractory multiple myeloma at the time of this analysis; progression-free survival benefit with ixazomib-Rd versus placebo-Rd did not translate into a statistically significant OS benefit on intent-to-treat analysis. OS benefit was greater in subgroups with adverse prognostic factors. OS interpretation was confounded by imbalances in subsequent therapies received, especially PIs and daratumumab.
3rd Department of Internal Medicine Semmelweis University Budapest Hungary
Arnie Charbonneau Cancer Research Institute University of Calgary Calgary Canada
Center of Oncology of the Lublin Region St Jana z Dukli Lublin Poland
Cross Cancer Institute University of Alberta Edmonton Canada
Department of Experimental Haematooncology Medical University of Lublin Lublin Poland
Department of Haematology Christchurch Hospital Christchurch New Zealand
Department of Haematology Middlemore Hospital Auckland New Zealand
Department of Haematology Palmerston North Hospital Palmerston North New Zealand
Department of Hematology Institut Paoli Calmettes Marseille France
Department of Hematology Skåne University Hospital Lund Sweden
Department of Hematology University Hospital Rigshospitalet Copenhagen Denmark
Division of Hematology Mayo Clinic Rochester MN
Hematology and Oncology University Hospital Brno Brno Czech Republic
Hôpital Pitié Salpêtrière Paris France
IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Bologna Italy
Medical Oncology Dana Farber Cancer Institute Boston MA
Millennium Pharmaceuticals Inc Cambridge MA
References provided by Crossref.org
ClinicalTrials.gov
NCT01564537
