title: Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.
abstract: 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.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Tamás
authors.initials: T
authors.lastname: Masszi
authors.forename: Ivan
authors.initials: I
authors.lastname: Špička
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.forename: Roman
authors.initials: R
authors.lastname: Hájek
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
authors.forename: Georgi G
authors.initials: GG
authors.lastname: Mihaylov
authors.forename: Vesselina
authors.initials: V
authors.lastname: Goranova-Marinova
authors.forename: Péter
authors.initials: P
authors.lastname: Rajnics
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Suvorov
authors.forename: Ruben
authors.initials: R
authors.lastname: Niesvizky
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Jakubowiak
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San-Miguel
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Vladimír
authors.initials: V
authors.lastname: Maisnar
authors.forename: Jiri
authors.initials: J
authors.lastname: Minarik
authors.forename: William I
authors.initials: WI
authors.lastname: Bensinger
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Dina
authors.initials: D
authors.lastname: Ben-Yehuda
authors.forename: Vishal
authors.initials: V
authors.lastname: Kukreti
authors.forename: Naseem
authors.initials: N
authors.lastname: Zojwalla
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Tonda
authors.forename: Xinqun
authors.initials: X
authors.lastname: Yang
authors.forename: Biao
authors.initials: B
authors.lastname: Xing
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D009842:Oligopeptides; D013792:Thalidomide; C524865:carfilzomib; D003907:Dexamethasone; D000077269:Lenalidomide