Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma
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- 8 January 2015
- journal article
- research article
- Published by Massachusetts Medical Society in New England Journal of Medicine
- Vol. 372 (2), 142-152
- https://doi.org/10.1056/nejmoa1411321
Abstract
Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan–Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk–benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.)Keywords
This publication has 33 references indexed in Scilit:
- Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myelomaBlood, 2013
- Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studiesHaematologica, 2013
- Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2Blood, 2011
- Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trialThe Lancet Oncology, 2009
- Criteria for diagnosis, staging, risk stratification and response assessment of multiple myelomaLeukemia, 2008
- Improved survival in multiple myeloma and the impact of novel therapiesBlood, 2008
- Lenalidomide plus Dexamethasone for Relapsed Multiple Myeloma in North AmericaNew England Journal of Medicine, 2007
- Lenalidomide plus Dexamethasone for Relapsed or Refractory Multiple MyelomaNew England Journal of Medicine, 2007
- CRITERIA FOR EVALUATING DISEASE RESPONSE AND PROGRESSION IN PATIENTS WITH MULTIPLE MYELOMA TREATED BY HIGH‐DOSE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATIONBritish Journal of Haematology, 1998
- The European Organization for Research and Treatment of Cancer QLQ-C30: A Quality-of-Life Instrument for Use in International Clinical Trials in OncologyJNCI Journal of the National Cancer Institute, 1993