Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu klinické zkoušky, fáze III, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
PubMed
34111952
DOI
10.1200/jco.21.00972
Knihovny.cz E-zdroje
- MeSH
- analýza přežití MeSH
- dexamethason aplikace a dávkování škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- glycin aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- kvalita života MeSH
- lenalidomid aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom farmakoterapie mortalita patologie MeSH
- následné studie MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- senioři MeSH
- sloučeniny boru aplikace a dávkování škodlivé účinky MeSH
- staging nádorů MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- dexamethason MeSH
- glycin MeSH
- ixazomib MeSH Prohlížeč
- lenalidomid MeSH
- sloučeniny boru 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
Citace poskytuje Crossref.org
ClinicalTrials.gov
NCT01564537
