BACKGROUND: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. METHODS: We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib withlenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. RESULTS: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. CONCLUSIONS: 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.).
RCT Entities:
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).
Authors: Paul G Richardson; Sundar Jagannath; Philippe Moreau; Andrzej J Jakubowiak; Marc S Raab; Thierry Facon; Ravi Vij; Darrell White; Donna E Reece; Lotfi Benboubker; Jeffrey Zonder; L Claire Tsao; Kenneth C Anderson; Eric Bleickardt; Anil K Singhal; Sagar Lonial Journal: Lancet Haematol Date: 2015-11-16 Impact factor: 18.959
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Authors: S Ailawadhi; J R Mikhael; B R LaPlant; K M Laumann; S Kumar; V Roy; D Dingli; P L Bergsagel; F K Buadi; S V Rajkumar; R Fonseca; M A Gertz; P Kapoor; T Sher; S R Hayman; A K Stewart; A Dispenzieri; R A Kyle; W I Gonsalves; C B Reeder; Y Lin; R S Go; N Leung; T Kourelis; J A Lust; S J Russell; A A Chanan-Khan; M Q Lacy Journal: Leukemia Date: 2017-09-01 Impact factor: 11.528
Authors: Jatin J Shah; Edward A Stadtmauer; Rafat Abonour; Adam D Cohen; William I Bensinger; Cristina Gasparetto; Jonathan L Kaufman; Suzanne Lentzsch; Dan T Vogl; Christina L Gomes; Natalia Pascucci; David D Smith; Robert Z Orlowski; Brian G M Durie Journal: Blood Date: 2015-09-17 Impact factor: 22.113