Multiple Myeloma Staging

Staging for multiple myeloma does not use the TNM system. Instead, the following systems are commonly used to characterize the bulk and aggressiveness of the disease:

• International Myeloma Working Group (IMWG) diagnostic criteria ^[1]  
• International Staging System (ISS) ^[2]
• Revised International Staging System(R-ISS) ^[3]

International Myeloma Working Group diagnostic criteria

The IMWG has established definitions of multiple myeloma and smoldering multiple myeloma. Multiple myeloma is defined as clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma, and one or more myeloma-defining events and biomarkers of malignancy.

A myeloma-defining event consists of evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically any of the following:

• Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL)
• Renal insufficiency: creatinine clearance <  40 mL per min or serum creatinine > 177 μmol/L (> 2 mg/dL)
• Anemia: hemoglobin value of > 20 g/L below the lower limit of normal, or a hemoglobin value <  100 g/L
• Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT

Biomarkers of malignancy are as follows:

• Clonal bone marrow plasma cell percentage ≥60%
• Involved:uninvolved serum free light chain ratio ≥100
• More than 1 focal lesion on MRI studies

To meet the definition of smoldering multiple myeloma, both of the following criteria must be met:

• Serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 h and/or clonal bone marrow plasma cells 10–60%
• Absence of myeloma-defining events or amyloidosis

International Staging System

ISS stages are as follows:

• Stage I: Serum beta-2 microglobulin <  3.5 mg/L and serum albumin ≥3.5 g/dL
• Stage II: Not stage I or stage III
• Stage III: Serum beta-2 microglobulin ≥ 5.5 mg/L

Revised International Staging System

R-ISS stages are as follows:

• Stage I: ISS stage I and  standard-risk chromosomal abnormalities by fluorescence in situ hybridization (FISH)(ie, no high-risk) and serum lactate dehydrogenase (LDH) level at or below the upper limit of normal
• Stage II: Not R-ISS stage I or III
• Stage III: ISS stage III and  either high-risk chromosomal abnormalities by FISH (ie, presence of del(17p) and/or translocation t(4;14) and/or translocation t(14;16)) or serum LDH level above the upper limit of normal