Significance of the MGUS-Like Phenotype in Patients With Multiple Myeloma and Light Chain Amyloidosis

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In a study reported in the Journal of Clinical Oncology, Burgos et al developed an algorithm to identify patients with multiple myeloma and light-chain amyloidosis who have the monoclonal gammopathy of undetermined significance (MGUS)-like phenotype, as well as identified the association of the phenotype with distinct outcomes in these patients.

Study Details

In the study, involving several multi-institutional cohorts, an algorithm to identify patients with the MGUS-like phenotype was developed on the basis of percentages of total bone marrow plasma cells and of clonal plasma cells within the bone marrow plasma cell compartment at the time of diagnosis. These were determined using flow cytometry in 548 patients with MGUS and 2,011 patients with active multiple myeloma. The clinical significance of the algorithm was assessed in cohorts of patients with smoldering multiple myeloma, active multiple myeloma, and light chain amyloidosis.

Key Findings

In a cohort of 246 patients with untreated smoldering multiple myeloma, 18% were classified as having the MGUS-like phenotype. Among these patients, the 2-year progression rate was 4.5%, compared with 28% and 63% among patients with smoldering multiple myeloma classified as intermediate and multiple myeloma–like (overall P < .001).

In a cohort of 1,525 newly diagnosed patients with active multiple myeloma enrolled in clinical trials, 7% were classified as having the MGUS-like phenotype. On multivariate analysis, patients with the MGUS-like phenotype had significantly better progression-free survival (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.32–0.74, P = .0001) and overall survival (HR = 0.56, 95% CI = 0.32–0.97, P = .039) compared to patients without the phenotype. Transplant-eligible patients (n = 780) with the MGUS-like phenotype had 5-year progression-free survival of 79% and 5-year overall survival of 96%; in this subgroup, no differences in progression-free or overall survival were observed according to complete remission and measurable residual disease status.

Classification of two cohorts of patients with light chain amyloidosis into MGUS-like, intermediate, and multiple myeloma–like phenotypes showed median progression-free survival of 47 months, 20 months, and 1 month (P = .001) and 23, 12, and 3 months (P < .001).

The MGUS-like calculator based on the algorithm is available at

The investigators concluded, “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 multiple myeloma and light chain amyloidosis.”

Bruno Paiva, PhD, of Clínica Universidad de Navarra, Pamplona, Spain, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Centro de Investigación Biomédica en Red del Instituto de Salud Carlos III, Cancer Research UK, and others. For full disclosures of the study authors, visit


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