Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance–Like Phenotype in Patients With Monoclonal Gammopathies

Abstract

PURPOSE The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)–like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated. PATIENTS AND METHODS An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis. RESULTS Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; P = .001) and overall survival (OS; HR, 0.56; P = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival. CONCLUSION We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.

The evolving pattern of the monoclonal protein improves the IMWG 2/20/20 classification for patients with smoldering multiple myeloma

“…In a recent study, BMPC flow cytometry parameters were used to classify patients and identified a group of SMM (18%) with an “MGUS‐like” phenotype and a 4.5% risk of progression. 2 The use of risk scores in the management of SMM can help identify individuals at high risk for progression and guide the decision‐making process regarding the initiation of treatment. The current treatment approach for all patients is watchful waiting irrespective of the risk level, but several attempts to treat high‐risk patients have been made in the context of clinical trials.…”

“…SMM is a heterogeneous disease, which includes patients with an “MGUS‐like” illness that will not progress to MM and patients with a rapidly progressive disease. In a recent study, BMPC flow cytometry parameters were used to classify patients and identified a group of SMM (18%) with an “MGUS‐like” phenotype and a 4.5% risk of progression 2 . The use of risk scores in the management of SMM can help identify individuals at high risk for progression and guide the decision‐making process regarding the initiation of treatment.…”

“…SMM constitutes a heterogeneous clinicopathological entity with some patients showing an indolent course (“MGUS‐like”) while others have a more aggressive behavior with a rapid progression to MM (“early MM”). 2 , 3 Retrospective studies have shown that the progression rate (PR) to MM is variable over time: 10% per year during the first 5 years, 3% per year for the next 5 years, and 1% thereafter. 4 …”