How I manage monoclonal gammopathy of undetermined significance

Ronald S. Go and S. Vincent Rajkumar


Monoclonal gammopathy of undetermined significance (MGUS) is, in many ways, a unique hematologic entity. Unlike most hematologic conditions in which the diagnosis is intentional and credited to hematologists, the discovery of MGUS is most often incidental and made by non-hematologists. MGUS is considered an obligate precursor to several lymphoplasmacytic malignancies including immunoglobulin light chain amyloidosis, multiple myeloma, and Waldenström macroglobulinemia. Therefore, long-term follow-up is generally recommended. Despite its high prevalence, there is surprisingly limited evidence to inform best clinical practice both at the time of diagnosis and during follow-up. We present seven vignettes to illustrate common clinical management questions that arise during the course of MGUS. Where evidence is present, we provide a concise summary of the literature and clear recommendations on management. Where evidence is lacking, we describe how we practice and provide a rationale for our approach. We also discuss the potential harms associated with MGUS diagnosis – a topic that is rarely, if ever, broached between patients and providers, or even considered in academic debate.

  • Submitted September 21, 2017.
  • Accepted November 19, 2017.