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25.2. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma

Chapter 25
Section Contents

Comprehensive guidelines on the classification of multiple myeloma (MM) and smouldering MM (SMM) were published in 2014 [42] and are outlined below. In contrast to earlier guidelines [583][584][115][27], the requirement for the presence of a monoclonal protein is no longer mandatory in the MM diagnostic criteria, to account for patients with nonsecretory MM (NSMM, Chapter 16). sFLC analysis is included and an involved/uninvolved Freelite sFLC ratio ≥100 is designated as a biomarker of malignancy (Table 25.1).

25.2.1. Definition of multiple myeloma

MM is defined by the presence of clonal bone marrow plasma cells (≥10%) or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events (Table 25.1) [42]:

Myeloma defining events Details
Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder

CRAB criteria:

Hypercalcaemia: 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)

Anaemia: haemoglobin value of >2 g/dL below the lower limit of normal, or a haemoglobin value <100 g/L

Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT

Any one or more of the following biomarkers of malignancy

▪ Clonal bone marrow plasma cell percentage ≥60%

▪ An involved/uninvolved sFLC ratio ≥100*

▪ >1 focal lesion on MRI studies

Table 25.1. Myeloma defining events [42]. *These values are based on the Freelite assay. The involved FLC must be ≥100 mg/L.

25.2.2. Definition of smouldering multiple myeloma

The definition of SMM requires that both of the following criteria must be met [42]:

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

25.2.3. Definition of monoclonal gammopathy of undetermined significance

The MM guidelines [42] also summarise the current definitions of monoclonal gammopathy of undetermined significance (MGUS) (Chapter 13) and these are listed below (Table 25.2):

MGUS type Definition (all criteria must be met)
Non-IgM MGUS

▪ Serum monoclonal protein (non-IgM type) <30 g/L

▪ Clonal bone marrow plasma cells <10%

▪ Absence of end-organ damage (such as hypercalcaemia, renal insufficiency, anaemia and bone lesions [CRAB features]) or amyloidosis that can be attributed to the plasma cell proliferative disorder

IgM MGUS

▪ Serum IgM monoclonal protein <30 g/L

▪ Bone marrow lymphoplasmacytic infiltration <10%

▪ No evidence of anaemia, constitutional symptoms, hyperviscosity, lymphadenopathy, hepatosplenomegaly, or other end-organ damage that can be attributed to the underlying lymphoproliferative disorder

Light chain MGUS

Abnormal FLC ratio (<0.26 or >1.65)

Increased level of the appropriate involved light chain (increased κ sFLCs in patients with ratio >1.65, and increased λ sFLCs in patients with ratio <0.26)

▪ No immunoglobulin heavy chain expression on immunofixation

▪ Absence of end-organ damage (such as CRAB features) or amyloidosis that can be attributed to the plasma cell proliferative disorder

▪ Clonal bone marrow plasma cells <10%

▪ Urinary monoclonal protein <500 mg/24 hours

Table 25.2. Categories of MGUS [42]. CRAB: hypercalcaemia, renal insufficiency, anaemia, bone lesions.