International Myeloma Working Group Diagnostic Criteria

Updated (2014) IMWG criteria for diagnosis of multiple myeloma and other monoclonal gammopathies

1. Assess for presence of a myeloma-defining event

  • Corrected calcium > 2.75 mmol/L or > 0.25 mmol/L higher than ULN, OR
  • Renal insufficiency (creatinine > 177 umol/L or CrCl < 40 mL/Min) due to light-chain cast nephropathy, OR
  • Hemoglobin < 10 g/dL or > 20 g/L below lower limit of normal, OR
  • One or more osteolytic lesions (≥ 5 mm) on X-ray, CT or PET-CT, OR
  • Clonal marrow plasma cells ≥ 60%*, OR
  • Ratio of uninvolved to involved serum free light chains ≥ 100 (provided involved free light chain is ≥ 100 mg/L), OR
  • > 1 focal lesion of ≥ 5 mm on MRI

* Assess clonality using flow cytometry or immunohistochemistry/fluorescence; bone marrow trephine biopsy preferred to assess plasma cell percentage. If discrepancy between aspirate and trephine, use the higher percentage.

2. Assess monoclonal protein and clonal plasma cells

DiagnosisMonoclonal proteinMarrow clonal plasma cellsMyeloma-defining event
Multiple myelomaAny level≥ 10%* (or histo­logically-proven plasma­cytomata)Present
Smolder­ing myeloma≥ 30 g/L (IgG or IgA) or urinary mono­clonal protein ≥ 500 mg/24h (and/or marrow criterion met)10% to 60% (and/or mono­clonal protein criterion met)Absent
Non-IgM mono­clonal gammo­pathy of uncertain signif­icance (MGUS)< 30 g/L (non-IgM)< 10%Absent
IgM MGUS< 30 g/L (IgM)< 10%**Absent
Light-chain MGUSAbnormal free light chain ratio AND raised involved light chain AND urinary mono­clonal protein < 500 mg/24h< 10%Absent
* If marrow clonal plasma cells < 10% but myeloma suspected, consider repeat biopsy
** < 10% lymphoplasmacytic cells in the case of IgM MGUS

Additional entities

AL amyloidosis

Amyloid-related symptoms, AND positive amyloid staining by Congo red in any tissue, AND light-chain nature of amyloid confirmed by mass-spectrometry or immunoelectronmicroscopy, AND presence of a monoclonal plasma cell disorder (monoclonal protein in serum or urine, abnormal free light chain ratio or clonal plasma cells in marrow)

Solitary plasmacytoma

Single bone or soft tissue lesion with clonal plasma cells on biopsy. No marrow clonal plasma cells. No other lesions on skeletal survey and on cross-sectional imaging (CT or MRI) spine & pelvis. No myeloma-defining event.

Solitary plasmacytoma with minimal marrow involvement

As for solitary plasmacytoma, but < 10% clonal plasma cells in marrow.

POEMS syndrome

Polyneuropathy, AND monoclonal plasma cell disorder (usually lambda), AND one major criterion AND one minor criterion. Major criteria: sclerotic bone lesions, Castleman’s disease, elevated VEGF. Minor criteria: organomegaly, fluid overload, endocrine dirder (other than diabetes or hypothyroidism), skin changes, papilloedema, thrombocytosis or erythrocytosis

Osteosclerotic multiple myeloma

International Myeloma Working Group Consensus diagnostic criteria for myeloma and monoclonal gammopathies were originally published in 2003, and were updated in 2014.1

CrCl: creatinine clearance
MGUS: monoclonal gammopathy of uncertain significance
MRI: magnetic resonance imaging
PET-CT: positron emission tomography with computed tomography
POEMS: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes
ULN: upper limit of normal
VEGF: vascular endothelial growth factor alpha