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Assessing Risk for Progression in Smoldering Myeloma

SM patients at the highest risk might benefit from therapy to prevent overt myeloma.

The plasma-cell dyscrasias encompass a spectrum of disorders, including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma, plasmacytoma, amyloidosis, and plasma-cell leukemia. An asymptomatic form, smoldering myeloma (SM), is defined by the presence of monoclonal paraprotein (an M-spike of >3 g/dL), bone-marrow plasmacytosis greater than 10%, or both, and absence of symptoms, anemia, lytic bone lesions, hypercalcemia, or renal insufficiency. Although most SM patients progress to overt myeloma or amyloidosis, the time course and risk factors for progression have not been well defined.

A Mayo Clinic group retrospectively reviewed medical records of 276 patients who were diagnosed with SM from 1970 through 1995; this cohort comprised 8% of all myeloma patients seen during that period. Rate of progression and correlates for development of overt myeloma or amyloidosis were identified. Marrow samples were reviewed for all patients; most patients had plasmacytosis of 15% to 19%. Three risk groups, stratified by M-spike and plasmacytosis proportion, were defined (M-spike only, plasmacytosis >10% only, or both).

Overall, 57% of SM patients developed active myeloma, and 2% developed amyloidosis, with a median time to progression of 4.8 years. Unlike MGUS, in which progression to myeloma occurs in about 1% of patients yearly during the first 20 years of follow-up, risk for progression of SM was 10% yearly during years 1 to 5, 3% yearly during years 6 to 10, and 1% yearly thereafter. Five-year median rates of disease progression for each group were: 15% for the M-spike–only group, 43% for >10%-plasmacytosis–only group, and 69% for the group with both. Multivariate analysis showed that risk factors for progression included both high serum paraprotein levels and high proportion of marrow plasma cells. Patients with IgA paraproteins had a higher risk for progression than did those with IgG paraproteins.

Comment: By definition, smoldering myeloma is asymptomatic, with patients traditionally followed for evidence of progression before initiation of therapy. As noted by the authors, further refinement of individual patient risk for progression from SM to overt myeloma might permit preventive therapeutic intervention for higher-risk patients. In particular, using FISH (fluorescence in situ hybridization) in the initial evaluation to identify biomarkers of lower or higher risk likely will enhance the predictive value of the clinical and laboratory parameters defined in this study.

— Michael E. Williams, MD

Published in Journal Watch Oncology and Hematology June 20, 2007

Citation(s):

Kyle RA et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007 Jun 21; 356:2582-90.

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