title: Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis.
abstract: OBJECTIVE
  Numerous studies have evaluated the prognostic value of minimal residual disease (MRD) in patients with multiple myeloma (MM). Most studies were small and varied in terms of patient population, treatment, and MRD assessment methods.
  
  
  OBJECTIVE
  To evaluate the utility of MRD detection in patients with newly diagnosed MM.
  
  
  METHODS
  A Medline search was conducted for articles published in English between January 1990 and January 2016.
  
  
  METHODS
  Eligible studies reported MRD status and progression-free survival (PFS) or overall survival (OS) in 20 or more patients following treatment. Among 405 articles identified, 21 met the initial eligibility criteria and were included in the analysis.
  
  
  METHODS
  Information on patient characteristics, treatment, MRD assessment, and outcomes were extracted using a standard form.
  
  
  METHODS
  The impact of MRD status on PFS and OS was assessed by pooling data from relevant trials. Data were adjusted to allow for different proportions of patients with MRD in different studies, and analyzed using the Peto method. Forest plots were created based on Cox model analysis. Other prespecified research questions were addressed qualitatively.
  
  
  RESULTS
  Fourteen studies (n = 1273) provided data on the impact of MRD on PFS, and 12 studies (n = 1100) on OS. Results were reported specifically in patients who had achieved conventional complete response (CR) in 5 studies for PFS (n = 574) and 6 studies for OS (n = 616). An MRD-negative status was associated with significantly better PFS overall (hazard ratio [HR], 0.41; 95% CI, 0.36-0.48; P < .001) and in studies specifically looking at CR patients (HR, 0.44; 95% CI, 0.34-0.56; P < .001). Overall survival was also favorable in MRD-negative patients overall (HR, 0.57; 95% CI, 0.46-0.71; P < .001) and in CR patients (HR, 0.47; 95% CI, 0.33-0.67; P < .001). Tests of heterogeneity found no significant differences among the studies for PFS and OS.
  
  
  CONCLUSIONS
  Minimal residual disease-negative status after treatment for newly diagnosed MM is associated with long-term survival. These findings provide quantitative evidence to support the integration of MRD assessment as an end point in clinical trials of MM.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.affiliation: Unit for Genomics in Myeloma, Institut Universitaire du Cancer, Toulouse, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Avet-Loiseau
authors.affiliation: St James's University Hospital, Leeds, United Kingdom.
authors.forename: Andy C
authors.initials: AC
authors.lastname: Rawstron
authors.affiliation: St James's University Hospital, Leeds, United Kingdom.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
authors.affiliation: University of Leeds, Leeds, United Kingdom.
authors.forename: J Anthony
authors.initials: JA
authors.lastname: Child
authors.affiliation: Celgene Corporation, Summit, New Jersey.
authors.forename: Anjan
authors.initials: A
authors.lastname: Thakurta
authors.affiliation: Celgene International, Boudry, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Sherrington
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Mehmet Kemal
authors.initials: MK
authors.lastname: Samur
authors.affiliation: Excerpta Medica, Amsterdam, the Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Georgieva
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: University of Leeds, Leeds, United Kingdom.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Gregory
mesh_terms: D015415:Biomarkers; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology*; D018365:Neoplasm, Residual / Q000473:pathology*; D011379:Prognosis; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers