title: The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma.
abstract: OBJECTIVE
  Multiple myeloma (MM) is consistently preceded by the precursor state, monoclonal gammopathy of undetermined significance (MGUS). The average annual risk of progression from MGUS to multiple myeloma is 0.5% to 1.0%. Current guidelines suggest life-long clinical follow-up of individuals diagnosed as having MGUS depending on risk stratification. The impact of diagnosing and conducting clinical follow-up of MGUS on MM survival is unclear.
  
  
  OBJECTIVE
  To estimate the impact of prior knowledge of MGUS diagnosis and comorbidities on MM survival.
  
  
  METHODS
  We conducted a population-based study including all patients with MM (MM patients) diagnosed in Sweden (n = 14,798) from 1976 to 2005 (with follow-up until 2007); 394 (2.7%) had previously been diagnosed as having MGUS. Information on comorbidities was gathered for all patients. We calculated survival rates from the time of MM diagnosis, comparing patients with vs those without prior knowledge of MGUS. Using Cox proportional hazards models, we calculated hazard ratios (HRs) and 95% CIs for risk factors for death. χ2 Tests were used to evaluate differences in comorbidities.
  
  
  METHODS
  Prior knowledge of MGUS among MM patients. In a subanalysis, monoclonal (M)-protein concentration and type were used as exposure.
  
  
  METHODS
  Risk of death and comorbidities.
  
  
  RESULTS
  Patients with MM with prior knowledge of MGUS had significantly (HR, 0.86; 95% CI, 0.77-0.96; P < .01) better overall survival (median survival, 2.8 years) than MM patients without prior knowledge of MGUS (median survival, 2.1 years), although MM patients with (vs without) prior knowledge of MGUS had more comorbidities (P < .001). Among MM patients with prior knowledge of MGUS, low M-protein concentration (<0.5 g/dL) at MGUS diagnosis was associated with poorer MM survival (HR, 1.86; 95% CI, 1.13-3.04; P = .01).
  
  
  CONCLUSIONS
  Patients with MM with prior knowledge of MGUS had better MM survival, suggesting that earlier treatment of MM leads to better survival. The observation that a low M-protein concentration at MGUS diagnosis was associated with poorer MM survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in patients with MGUS, regardless of risk stratification.
authors.affiliation: Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Elin Edda
authors.initials: EE
authors.lastname: Sigurdardottir
authors.affiliation: Department of Hematology and Coagulation Disorders, Skane University Hospital, Malmö, Sweden.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
authors.affiliation: Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Sigrun Helga
authors.initials: SH
authors.lastname: Lund
authors.affiliation: Division of Hematology, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ebba K
authors.initials: EK
authors.lastname: Lindqvist
authors.affiliation: Multiple Myeloma Section, Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Sham
authors.initials: S
authors.lastname: Mailankody
authors.affiliation: Multiple Myeloma Section, Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Neha
authors.initials: N
authors.lastname: Korde
authors.affiliation: Division of Hematology, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.affiliation: Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
authors.affiliation: Faculty of Medicine, University of Iceland, Reykjavik, Iceland3Division of Hematology, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sigurdur Y
authors.initials: SY
authors.lastname: Kristinsson
mesh_terms: D016009:Chi-Square Distribution; D015897:Comorbidity; D018450:Disease Progression; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000175:diagnosis* / Q000453:epidemiology* / Q000401:mortality / Q000628:therapy; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000453:epidemiology* / Q000401:mortality / Q000628:therapy; D011159:Population Surveillance; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors