IMWG Diagnostic Criteria for Multiple Myeloma and Related Plasma Cell Disorders

Plasma cell neoplasms including multiple myeloma (MM) and related terminally differentiated B-cell neoplasms are characterized by secretion of monoclonal immunoglobulin and stepwise development from a preneoplastic clonal B and/or plasma cell proliferation called monoclonal gammopathy of undetermined significance (MGUS). Diagnosis of these disorders requires integration of clinical, laboratory, and morphological features.

International Myeloma Working Group Diagnostic Criteria for Multiple Myeloma and Related Plasma Cell Disorders

Disorder	Disease Definition
Non-IgM MGUS	All three criteria must be met: Serum monoclonal protein (non-IgM type) < 3 g/dL Clonal bone marrow plasma cells < 10%* Absence of end-organ damage such as CRAB features that can be attributed to the plasma cell proliferative disorder
Smoldering MM	Both criteria must be met: Serum monoclonal protein (IgG or IgA) ≥ 3 gm/dL, 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
MM	Both criteria must be met: Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma Any one or more of the following myeloma defining events: Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: 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/min or serum creatinine > 177 mmol/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 lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT Clonal bone marrow plasma cell percentage ≥ 60% Involved: uninvolved serum FLC ratio ≥ 100 (involved FLC level must be ≥ 100 mg/L) > 1 focal lesion on MRI studies (at least 5 mm in size)
IgM MGUS	All three criteria must be met: Serum IgM monoclonal protein < 3 g/dL Bone marrow lymphoplasmacytic infiltration < 10% No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder.
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 kappa FLC in patients with ratio > 1.65 and increased lambda FLC in patients with ratio < 0.26) No immunoglobulin heavy-chain expression on immunofixation Absence of end-organ damage that can be attributed to the plasma cell proliferative disorder Clonal bone marrow plasma cells < 10% Urinary monoclonal protein < 500 mg/24 h
Solitary Plasmacytoma	All four criteria must be met: 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 (or CT) of spine and pelvis (except for the primary solitary lesion) Absence of end-organ damage such as CRAB features that can be attributed to a lympho-plasma cell proliferative disorder
Solitary Plasmacytoma With Minimal Marrow Involvement**	All four criteria must be met: Biopsy-proven solitary lesion of bone or soft tissue with evidence of clonal plasma cells Clonal bone marrow plasma cells < 10% Normal skeletal survey and MRI (or CT) of spine and pelvis (except for the primary solitary lesion) Absence of end-organ damage such as CRAB features that can be attributed to a lympho-plasma cell proliferative disorder

 

Abbreviations: MGUS, monoclonal gammopathy of undertermined significance; CRAB features, hypercalcemia, renalinsufficiency, anemia, and bone lesions; MM, multiple myeloma; FLC, freelight chain; SMM, smoldering multiple myeloma.
*A bone marrow examination can be deferred for patients with low-risk MGUS (IgG type, M protein < 15 g/L, normal FLC ratio) in whom there are no clinical features concerning for myeloma.
**Solitary plasmacytoma with 10% or more clonal plasma cells is considered as MM.

 

References:

1. Fend F, Dogan A, Cook JR. Plasma cell neoplasms and related entities-evolution in diagnosis and classification. Virchows Arch. 2023 Jan;482(1):163-177. [Medline]
2. Rajkumar SV. Updated Diagnostic Criteria and Staging System for Multiple Myeloma. Am Soc Clin Oncol Educ Book. 2016;35:e418-23. [Medline]

 

Created Nov 14, 2023.