title: Effects of lenalidomide and dexamethasone treatment duration on survival in patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone.
abstract: BACKGROUND
  In two randomized phase III trials (MM-009 and MM-010), lenalidomide plus dexamethasone significantly prolonged time to progression and overall survival (OS) in patients with relapsed/refractory multiple myeloma compared with dexamethasone alone. In both trials the treatment was continued until disease progression or unacceptable toxicity. We conducted a subanalysis to determine if continuing therapy after achieving≥partial response (PR) improved survival.
  
  
  METHODS
  Data were collected on 212 patients who were treated with lenalidomide plus dexamethasone and achieved≥PR. Kaplan-Meier survival estimates were compared between patients on continued treatment versus patients discontinuing therapy because of adverse events, withdrawal of consent, or other reasons. Time-dependent multivariate regression analyses were used to determine the benefit of continuing treatment with lenalidomide.
  
  
  RESULTS
  A total of 174 patients received continued treatment until disease progression or death, and 38 patients discontinued therapy without progression. There was a trend toward longer median OS in patients who continued therapy (50.9 months vs. 35.0 months; P=.0594). When controlling for the number of previous antimyeloma therapies, β2-microglobulin levels, and Durie-Salmon stage (which adversely affected survival in these patients), continued lenalidomide treatment (HR, 0.137; 95% CI, 0.045-0.417; P=.0005) or each additional cycle of lenalidomide (HR, 0.921; 95% CI, 0.886-0.957; P<.0001) were both associated with longer survival.
  
  
  CONCLUSIONS
  Continued lenalidomide treatment until disease progression after achievement of ≥PR is associated with a significant survival advantage when controlling for patient characteristics. These findings should be confirmed in a prospectively designed trial.
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, CIC, IBMCC, Spain. sanmigiz@usal.es
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San-Miguel
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: David
authors.initials: D
authors.lastname: Siegel
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Bravo
authors.forename: Marta
authors.initials: M
authors.lastname: Olesnyckyj
authors.forename: Robert D
authors.initials: RD
authors.lastname: Knight
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Donna M
authors.initials: DM
authors.lastname: Weber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide