Multiple myeloma diagnostic criteria

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]; Serge Korjian M.D.; Shyam Patel [3]

The diagnosis of monoclonal gammopathy of undetermined significance requires the presence of clonal plasma cells < 10% and serum monoclonal protein <3g/dl but the absence of end-organ damage. The diagnosis of smoldering multiple myeloma requires the presence of clonal plasma cells 10%-60% and serum monoclonal protein >3g/dl but the absence of end-organ damage. The diagnosis of active multiple myeloma requires the presence of end-organ damage. In November 2014, the International Myeloma Working Group (IMWG) updated the criteria for the diagnosis of multiple myeloma to include novel validated biomarkers to better encompass the extent of disease. Prior to 2014, the original diagnostic criteria for end-organ damage included CRAB features (hypercalcemia, renal failure, anemia, and bone lesions) without consideration of the plasma cell burden or free light chain ratio. The 2014 update also clarified the underlying laboratory and radiographic findings of CRAB features, as well as the histological and monoclonal protein requirements for the disease diagnosis.^[1]

The diagnosis of multiple myeloma requires the following:^[1][2][3][4]

• ≥10% clonal plasma cells in bone marrow

OR

• biopsy-proven bony or extramedullary plasmacytoma,

With one or more of the myeloma-defining events:

• CRAB features:
  • 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 >2 g/dL below the lower limit of normal, or a hemoglobin value <10 g/dL
  • Bone lesion: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT
• Biomarkers of malignancy:
  • Bone marrow plasma cell burden: Clonal bone marrow plasma cell percentage ≥60%
  • Free light chain ratio: Involved-to-uninvolved free light chain ratio ≥100
  • MRI: >1 focal bony lesion of 5mm or greater on MRI studies

All three criteria must be met:^[1][2][3]

• Presence of serum monoclonal protein (IgG or IgA) <3 g/dL
• Presence of bone marrow clonal plasma cells <10%
• Absence of multiple myeloma-defining events or amyloidosis

Both criteria must be met:^[1][2]

• Serum monoclonal protein (IgG or IgA) ≥3 g/dL or urinary monoclonal protein ≥500 mg per 24 h and/or clonal bone marrow plasma cells 10–60%
• Absence of multiple myeloma-defining events or amyloidosis

All four criteria must be met:^[2]

• Biopsy-proven solitary lesion of bone or soft tissue with evidence of clonal plasma cells
• Normal bone marrow with no evidence of clonal plasma cells
• Normal skeletal survey and MRI of spine and pelvis (except for the primary solitary lesion)
• No evidence of end-organ damage such as CRAB lesions that can be attributed to a lymphoplasma cell proliferative disorder