title: The road to cure in multiple myeloma starts with smoldering disease.
abstract: BACKGROUND
  Smoldering multiple myeloma (SMM) is a heterogeneous clinical entity that defines patients in the spectrum of disease progression from monoclonal gammopathy of undetermined significance to multiple myeloma (MM). Current standard of care is observation until end organ damage occurs. In spite of this, the scientific community has begun to question whether the strategy of watchful waiting should be replaced with earlier therapeutic intervention with the ultimate goal of preventing clonal heterogeneity and end organ damage.
  
  
  METHODS
  In this review, we challenge the concept of observation as the best option of therapy in SMM. We present current data on diagnosis, prognostic factors of disease progression and studies that have been conducted to date to determine whether earlier therapeutic interventions will lead to an improvement in overall survival of patients with MM.
  
  
  CONCLUSIONS
  If the recommendations of treatment of SMM were to change, the scientific body of evidence would have to overcome four major hurdles: to demonstrate that early intervention leads to prolonged survival and delay in development of end organ damage, that it does not have long-term toxicities, that it is implemented in patients with a high-likelihood of developing myeloma and that it does not lead to the outgrowth of more resistant clones. Only well-designed clinical trials will determine whether cure can be achieved with earlier interventions.
authors.forename: Karma Z
authors.initials: KZ
authors.lastname: Salem
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
keywords: early treatment; multiple myeloma; precursor disease; prevention of progression; prognosis; risk factors of progression; smoldering myeloma