Monoclonal gammopathy of increasing significance: time to screen?

Abstract

Monoclonal gammopathy (MG) is a frequently detected clonal B-cell or plasma-cell disorder. Importantly, every multiple myeloma (MM) case is preceded by MG. Although clinical algorithms now allow earlier treatment of patients with biomarkers of malignancy before MM-induced tissue damage (CRAB) occurs, most patients are still diagnosed late. It is important to revisit how MG should be managed in clinical practice and whether screening is required. As the prevalence of MG and other medical co-morbidities both rise with increasing age, the degree of contribution of MG to disease states other than malignant progression is often unclear. This can lead to monitoring lapses and under recognition of the organ dysfunction that can occur with monoclonal gammopathy of clinical significance (MGCS). Therefore, models of progression to MM and/or MGCS require further refinement. While MG is currently detected incidentally, a case for screening has been made with ongoing studies in this area. Screening has the potential benefit of earlier detection and prevention of both MGCS and delayed MM presentations, but important drawbacks include the psychosocial impact on individuals and resource burden on healthcare services. MG terminology should transition alongside our increasing understanding of the condition and genomic characterization that have already begun to revise the MG nomenclature. The biology of MG has been poorly understood and is often inferred from the biology of MM, which is unhelpful. We review the literature and case for MG screening in this paper. In particular, we highlight areas that require focus to establish screening for MG.

Figure 1.

Proposed schema for classification of monoclonal gammopathies. ^§The cell intrinsic/extrinsic factors that lead to the persistence and/or progression of plasma/B-cell clones are still unknown. *The events, e.g. genomic/proteomic changes, defining monoclonal gammopathy of clinical significance have not yet been defined and require further research. "'"Myeloma-defining events have recently been described. ^AThe interplay and relationship between benign monoclonal gammopathy, monoclonal gammopathy of clinical significance and multiple myeloma/Waldenström macroglobulinemia is not fully understood; it is not clear whether the genomic and biological drivers of these conditions are shared or distinct. MG: monoclonal gammopathy; MDE: myeloma-defining event; MGCS: monoclonal gammopathy of clinical significance; MM: multiple myeloma; WM: Waldenström macroglobulinemia.