Monoclonal gammopathy of undetermined significance in medical hospital admissions - a new strategy for screening?

Abstract

Monoclonal gammopathy of undetermined significance (MGUS), is a common clonal plasma cell disorder with a prevalence that increases with age up to 3·2% in those aged >50 years in population-based screening studies (Kyle et al., 2006). It is a precursor of myeloma and certain other lymphoproliferative diseases, with a risk of progression of about 1% per year. Also, in the absence of malignant transformation MGUS may be associated with complications that motivate further examination and treatment (Go & Rajkunar, 2018). Most studies on MGUS, including risk factors for progression and association with comorbidities, have been done in patients where serum protein electrophoresis was performed during the medical evaluation of various symptoms and constitute a selected population. In this journal, Catherine Atkins and coworkers present data on the prevalence of MGUS in unselected emergency medical hospital admissions. After obtaining informed consent, serum samples were collected and M protein identified by protein electrophoresis and immunofixation. The study by Atkins et al. has produced some interesting data (Atkins et al., 2020). First, they show that the prevalence of MGUS is considerably higher in this group than reported in a large study based on population screening (Kyle et al., 2006). There is a debate on the pros and cons of population screening for MGUS, considering on one hand the need for early diagnosis of myeloma, and on the other hand the overall low risk of progression, the impact on healthcare resources and concern that the diagnosis of MGUS might cause unneccessary anxiety (Go & Rajkunar, 2018). The present study suggests that patients admitted to an emergency unit might represent a select population for screening with a favourable health economy compared to screening of the general population. The authors have also attempted to find explanations for the increased prevalence by studying reasons for admission and comorbidity. Unfortunately, the number of cases is too low to draw any definite conclusions. However, some interesting associations are reported including comorbidities such as heart failure and chronic kidney disease. Although no cases of light-chain (AL)-amyloidosis or light-chain deposition disease were identified in the study, the follow-up is limited and the observation highlights the need to consider clinical characteristics to identify patients who should be further examined for M protein-related diseases. An interesting observation is that some patients had a previously detected M protein that was unknown to the patients and evidently was not acted upon. This indicates an unmet need for education about follow-up of MGUS. Although several clinical practice guidelines for risk stratification and follow-up have been published, the adherence to these is often low (Go et al., 2017). Current practical guidelines do not recommend population screening for MGUS or treatment of MGUS, but this can change. Ten years ago, only patients with symptomatic myeloma defined by CRAB criteria (C, hypercalcaemia; R, Renal insufficiency; A, Anaemia; B, Bone lesions) were treated, but now a number of studies indicate that patients with smouldering (asymptomatic) myeloma may benefit from treatment (Landgren, 2017). In the future, treatment of selected patients with MGUS with a high risk of progression may be considered. There is limited information on the effect of routine follow-up of MGUS on early diagnosis of multiple myeloma and on survival (Go et al., 2015; Sigurdardottir et al., 2015). A randomised controlled trial (iSTOPMM [Iceland Screens Treats or Prevents Multiple Myelom] study) is ongoing in Iceland, with the aim to assess the benefits and harms of population screening and follow-up of MGUS. Efforts to identify patient groups where screening for MGUS may be recommended are important.