Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations

Abstract

Purpose: To provide an overview on smoldering (asymptomatic) multiple myeloma (SMM) including current diagnostic criteria, predictors of progression, pattern of progression, and outcome.

Design: A comprehensive review of the literature on risk factors for progression, treatment attempts to delay progression and outcome in patients with SMM.

Results: The risk factors for progression of SMM include: plasma cell mass including M-protein size and percentage of bone marrow clonal plasma cells (BMPC), abnormal free light chain ratio, proportion of phenotypically abnormal BMPC, immunoparesis, evolution pattern (evolving v nonevolving), and pattern of magnetic resonance imaging abnormalities. Most patients with SMM progress with anemia and/or skeletal involvement. Immediate therapy with cytotoxic agents, such as melphalan/prednisone has not resulted in improved outcome. Patients should not be treated until progressive disease with end-organ damage occurs. Increasing anemia is the most reliable indicator of progression.

Conclusion: These recently recognized predictors of outcome may be helpful for better disease monitoring and for investigation of new treatment approaches. Thus, recommendations for follow-up every to 3 to 6 months depending on the risk of progression are suggested, and clinical trials with new noncytotoxic biologically derived agents to delay progression, particularly in high-risk patients, are ongoing.

Fig 1.

Probability of progression to active myeloma or primary amyloidosis in patients with smoldering multiple myeloma among three risk groups: group 1 (bone marrow plasma cells ≥ 10%, M-protein level ≥ 3 g/dL), group 2 (plasma cells ≥ 10%, M-protein level < 3 g/dL), and group 3 (plasma cells < 10%, M-protein level ≥ 3 g/dL). With permission of the New England Journal of Medicine, Kyle et al.

Fig 2.

Risk stratification based on bone marrow plasmacytosis, serum M protein, and serum immunoglobulin free-light chain (FLC) ratio. Patients are assigned 1 point for meeting each of the following criteria: bone marrow clonal plasma cells ≥ 10%; serum M protein ≥ 3 g/dL; and serum immunoglobulin FLC ratio either less than 0.125 or > 8. The median times to progression for 1, 2, or 3 risk factors are 10, 5.1, and 1.9 years, respectively. This research was originally published in Blood. Dispenzieri A, Kyle RA, Katzman JA, et al: Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 111:785-789, 2008. © American Society of Hematology.

Fig 3.

Evolution of the serum M-protein levels in patients with (A) evolving smoldering myeloma and (B) nonevolving myeloma. With permission of the British Journal of Hematology, Rosiñol et al. © Blackwell Publishing Ltd.

Fig 4.

Probability of progression to active myeloma or primary amyloidosis in patients with smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS). With permission of the New England Journal of Medicine, Kyle et al.