title: Residual serum monoclonal protein predicts progression-free survival in patients with previously untreated multiple myeloma.
abstract: BACKGROUND
  Currently used treatment response criteria in multiple myeloma (MM) are based in part on serum monoclonal protein (M-protein) measurements. A drawback of these criteria is that response is determined solely by the best level of M-protein reduction, without considering the serial trend. The authors hypothesized that metrics incorporating the serial trend of M-protein would be better predictors of progression-free survival (PFS).
  
  
  METHODS
  Fifty-five patients with measurable disease at baseline (M-protein > or = 1 g/dL) who received > or = 4 cycles of treatment from 2 clinical trials in previously untreated MM were included. Three metrics based on the percentage of M-protein remaining relative to baseline (residual M-protein) were considered: metrics based on the number of times residual M-protein fell within prespecified thresholds, metrics based on area under the residual M-protein curve, and metrics based on the average residual M-protein reduction between Cycles 1 and 4. The predictive value of these metrics was assessed in Cox models using landmark analysis.
  
  
  RESULTS
  The average residual M-protein reduction was found to be significantly predictive of PFS (P = .02; hazard ratio, 0.37), in which a patient with a 10% lower average residual M-protein reduction from Cycle 1 to 4 was estimated to be at least 2.7x more likely to develop disease progression or die early. None of the other metrics was predictive of PFS. The concordance index for the average residual M-protein reduction was 0.63, compared with 0.56 for best response.
  
  
  CONCLUSIONS
  The average residual M-protein reduction metric is promising and needs further validation. This exploratory analysis is the first step in the search for treatment-based trend metrics predictive of outcomes in MM.
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Schaefer
authors.forename: Shaji
authors.initials: S
authors.lastname: Kumar
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Allred
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Sumithra J
authors.initials: SJ
authors.lastname: Mandrekar
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood*; D009194:Myeloma Proteins / Q000032:analysis*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009194:Myeloma Proteins