Prognostic factors in smoldering multiple myeloma

Mayo 2018/IMWG risk stratification system (20/2/20 criteria):^[1,2]

Bone marrow plasma cells >20%
M protein >2 g/dL
Involved/uninvolved free light chain (FLC) ratio >20

Stratifies patients with SMM into populations with low (no factors present), intermediate (one factor present), and high (two or three factors present) risk of progression.

Other potential risk factors for progression identified in some but not all studies:^[3]

IgA SMM
Immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes
Abnormal plasma cell immunophenotype (≥95% of BMPCs are clonal) and reduction of ≥1 uninvolved immunoglobulin isotypes
Increased circulating plasma cells (by immunofluorescence or flow cytometry)
Progressive increase in M protein level (evolving type of SMM; increase in serum M protein by ≥25% on 2 successive evaluations within a 6-month period)
Clonal BMPCs 50 to 59%
t(4;14) or del(17p) or 1q gain
MRI with diffuse abnormalities or 1 focal lesion
PET-CT with focal lesion with increased uptake without underlying osteolytic bone destruction
Bence Jones proteinuria in IgG or IgA SMM

Smoldering multiple myeloma (SMM) is defined as a monoclonal (M) protein ≥3 g/dL and/or 10 to 59% bone marrow plasma cells but no end-organ damage (lytic lesions, anemia, kidney disease, or hypercalcemia) that can be attributed to the underlying plasma cell disorder and no other myeloma-defining events (ie, clonal bone marrow plasma cells ≥60%, serum free light chain (FLC) ratio ≥100 with measurable involved FLC level ≥100 mg/L, or >1 focal lesion on MRI scan), and no amyloidosis^[4].

BMPCs: bone marrow plasma cells; IgA: immunoglobulin A; IgG: immunoglobulin G; SMM: smoldering multiple myeloma; M protein: monoclonal protein; MRI: magnetic resonance imaging; PET-CT: positron emission tomography with computed tomography.

References:

Lakshman A, Rajkumar SV, Buadi FK, et al. Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J 2018; 8:59.
Mateos MV, Kumar S, Dimopoulos MA, et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J 2020; 10:102.
Rajkumar SV, Landgren O, Mateos MV. Smoldering multiple myeloma. Blood 2015; 125:3069.
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15:e538.

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Prognostic factors in smoldering multiple myeloma