title: Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the Medical Research Council Myeloma IX Study.
abstract: OBJECTIVE
  To investigate the prognostic value of minimal residual disease (MRD) assessment in patients with multiple myeloma treated in the MRC (Medical Research Council) Myeloma IX trial.
  
  
  METHODS
  Multiparameter flow cytometry (MFC) was used to assess MRD after induction therapy (n = 378) and at day 100 after autologous stem-cell transplantation (ASCT; n = 397) in intensive-pathway patients and at the end of induction therapy in non-intensive-pathway patients (n = 245).
  
  
  RESULTS
  In intensive-pathway patients, absence of MRD at day 100 after ASCT was highly predictive of a favorable outcome (PFS, P < .001; OS, P = .0183). This outcome advantage was demonstrable in patients with favorable and adverse cytogenetics (PFS, P = .014 and P < .001, respectively) and in patients achieving immunofixation-negative complete response (CR; PFS, P = .0068). The effect of maintenance thalidomide was assessed, with the shortest PFS demonstrable in those MRD-positive patients who did not receive maintenance and longest in those who were MRD negative and did receive thalidomide (P < .001). Further analysis demonstrated that 28% of MRD-positive patients who received maintenance thalidomide became MRD negative. MRD assessment after induction therapy in the non-intensive-pathway patients did not seem to be predictive of outcome (PFS, P = .1).
  
  
  CONCLUSIONS
  MRD assessment by MFC was predictive of overall outcome in patients with myeloma undergoing ASCT. This predictive value was seen in patients achieving conventional CR as well as patients with favorable and adverse cytogenetics. The effects of maintenance strategies can also be evaluated, and our data suggest that maintenance thalidomide can eradicate MRD in some patients.
authors.affiliation: St James's University Hospital, Leeds, United Kingdom.
authors.forename: Andy C
authors.initials: AC
authors.lastname: Rawstron
authors.forename: J Anthony
authors.initials: JA
authors.lastname: Child
authors.forename: Ruth M
authors.initials: RM
authors.lastname: de Tute
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.forename: Walter M
authors.initials: WM
authors.lastname: Gregory
authors.forename: Sue E
authors.initials: SE
authors.lastname: Bell
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szubert
authors.forename: Nuria
authors.initials: N
authors.lastname: Navarro-Coy
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.forename: Sylvia
authors.initials: S
authors.lastname: Feyler
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Ross
authors.forename: Gordon
authors.initials: G
authors.lastname: Cook
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001707:Biopsy, Needle; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018365:Neoplasm, Residual / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D012074:Remission Induction; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D013792:Thalidomide