| Type of monoclonal gammopathy | Premalignancy with low risk of progression (1 to 2 percent per year) | Premalignancy with high risk of progression (10 percent per year) | Malignancy |
| IgG and IgA (non-IgM)* | Non-IgM MGUS All criteria must be met: - Serum monoclonal protein <3 g/dL
- Clonal BM plasma cells <10 percent
- Absence of end-organ damage such as CRAB that can be attributed to the PCPD and absence of myeloma defining biomarkers
| Smoldering MM Both criteria must be met: - Serum monoclonal protein (IgG or IgA) ≥3 g/dL and/or clonal BM plasma cells ≥10 percent
- Absence of end-organ damage such as CRAB that can be attributed to a PCPD and absence of myeloma defining biomarkers
| MM Clonal BM plasma cells ≥10 percent Plus one of the following: - Evidence of end-organ damage that can be attributed to the underlying PCPD, specifically one or more of the following:
- Hypercalcemia: serum calcium ≥11.5 mg/dL
- Renal insufficiency: serum creatinine >2 mg/dL or estimated creatinine clearance <40 mL/min
- Anemia: normochromic, normocytic with hemoglobin >2 g/dL below lower limit of normal or hemoglobin <10 g/dL
- Bone lesions: lytic lesions ≥5 mm attributed to a PCPD on skeletal radiography, MRI, CT, or PET/CT
- Presence of one of the following biomarkers:
- ≥60 percent clonal plasma cells in bone marrow
- Involved/uninvolved FLC ratio ≥100
- MRI with >1 focal bone lesion
|
| IgM | IgM MGUSΔ All criteria must be met: - Serum monoclonal protein <3 g/dL
- Clonal BM lymphoplasmacytic cells <10 percent
- Absence of end-organ damage such as anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder
| Smoldering WM Both criteria must be met: - Serum IgM monoclonal protein ≥3 g/dL and/or BM lymphoplasmacytic infiltration ≥10 percent
- No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder
| WM All criteria must be met: - IgM monoclonal gammopathy (regardless of size of M protein)
- ≥10 percent BM lymphoplasmacytic infiltration (usual intertrabecular) by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation and a typical immunophenotype (eg, surface IgM+, CD5±, CD10–, CD19+, CD20+, CD23–) that satisfactorily excludes other lymphoproliferative disorders including chronic lymphocytic leukemia and mantle cell lymphoma
- Evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder
| IgM myeloma All criteria must be met: - Symptomatic monoclonal PCPD characterized by a serum IgM monoclonal protein regardless of size
- Presence of ≥10 percent plasma cells on BM biopsy
- Presence of lytic bone lesions related to the underlying plasma cell disorder and/or translocation t(11:14) on FISH
|
| Light chain | Light chain MGUS All criteria must be met: - Abnormal FLC ratio (<0.26 or >1.65)
- Increased level of the appropriate involved light chain (increased κ FLC in patients with ratio >1.65 and increased λ FLC in patients with ratio <0.26)
- No immunoglobulin heavy chain expression on immunofixation
- Clonal BM plasma cells <10 percent
- Absence of end-organ damage such as CRAB that can be attributed to the PCPD
| Idiopathic Bence Jones proteinuria All criteria must be met: - Urinary monoclonal protein on urine protein electrophoresis ≥500 mg/24 h and/or clonal BM plasma cells ≥10 percent
- No immunoglobulin heavy chain expression on immunofixation
- Absence of end-organ damage such as CRAB that can be attributed to the PCPD
| Light chain MMΔ Same as MM except no evidence of immunoglobulin heavy chain expression on immunofixation |
