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Statistics suggest that 3.2% of people aged 50 years or older and 5.3% of those aged 70 years or older have monoclonal gammopathy of undetermined significance (MGUS), the precursor disease to Multiple Myeloma (MM). Understanding the risk factors that determine progression to MM is a key area of research, as many physicians are now keen to move on from the ‘watch and wait’ philosophy, with the aim that earlier intervention in patients where high of progression can be identified will prevent MM taking hold in the first place. Due to the short follow-up times in many previous studies, it has been difficult to establish the risk of progression from MGUS to MM. There is also a paucity of data related to the prognosis and risk stratification in MGUS patients who are classified either with IgM or non-IgM biological subtypes.
Robert A. Kyle, and a team of highly esteemed colleagues from the Mayo Clinic, Rochester, Minnesota, US, conducted a long-term follow-up in which they assessed the rate of progression and survival in MGUS patients, who were classified as either IgM or non-IgM subtypes. The primary end-point of the study was progression to either MM, or any other plasma cell (PC) or lymphoid disorder (non-hodgkin’s lymphoma, AL amyloidosis, waldenstrom’s macroglobulinemia, chronic lymphocytic leukemia or plasmacytoma). The results were published in the New England Journal of Medicine in January 2018.
Significant differences were observed between both the IgM and non-IgM subtype of MGUS patients and the risk of progression, suggesting that identifying the biological subtype could help with monitoring and therapeutic strategy. Another key finding was the shorter survival rate in MGUS patients in comparison with the age- and sex-matched control population. However, a much lower risk of progression to MM and other related conditions was found in MGUS patients, in comparison to the risk of death due to other causes. This, therefore, strengthens the case for continuing with a 'watch and wait' approach for MGUS patients, at least until clearer genetic links and risk factors can be identified. The ongoing Icelandic study (iSTOPMM), which has recruited a large number of MGUS patients, should generate insightful data on ways to monitor and manage MGUS patients, in terms of progression to MM.
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