Both criteria must be met:

• Serum monoclonal protein (IgG or IgA) ≥ 30g/L or urinary monoclonal protein ≥ 500mg per 24h and/or clonal bone marrow plasma cells 10-60%

• Absence of myeloma-defining events or amyloidosis

Surveillance:

Patients with SMM have a higher risk of progression to myeloma than MGUS. The risk is highest in the first 2 years after diagnosis and decreases in the subsequent years. These patients should have SPEP, UPEP, complete blood count, and calcium and creatinine measured 2 to 3 months after the initial diagnosis. If the results are stable, the studies should be repeated every 4 to 6 months during the first year and, if stable, evaluation can be lengthened to every 6 to 12 months.

• Serum monoclonal protein <30g/L

• Clonal bone marrow plasma cells <10%

• Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) or amyloidosis that can be attributed to the plasma cell proliferative disorder

Currently, there is no evidence to screen the general population for MGUS. Risk-stratification models have been proposed for progression of MGUS and assist in detecting patients with higher risk of progression to myeloma, AL amyloidosis or Waldenström macroglobulinemia. Presence of an M protein ≥ 1.5 g/dL and an abnormal free light chain ratio are adverse predictors of long-term risk of progression. For patients with non-IgM MGUS, the risk of progression at 20 years is 30% among those with two risk factors, 20% among those so have only one risk factor, and only 7% among patients who had neither risk factor. For patients with IgM MGUS, presence of two adverse risk factors was associated with a risk of progression at 20 years of 55%, compared to 41% among those with one adverse factor and 19% among those with neither. Patients with MGUS should be monitored indefinitely without treatment because patients progress at a constant rate of approximately 1% per year. Low-risk patients do not require a bone marrow biopsy at diagnosis. Whole-body CT skeletal survey is recommended in patients with high-risk non-IgM MGUS. Patients should have SPEP, UPEP, and serum free light chains repeated 3 to 4 months after initial diagnosis and if stable can be followed every year for high- or intermediate-risk patients and every 2 to 3 years for low-risk patients (no risk factors present) or when myeloma symptoms arise. Treatment is not indicated unless it is part of a clinical trial.

Consider referral to the MGUS clinic in Kelowna.

• Serum IgM monoclonal protein <30g/L

• No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, hepatosplenomegaly, or other end-organ damage that can be attributed to the plasma cell proliferative disorder

• Abnormal FLC ratio (<0.26 or >1.65)

• Increased level of the appropriate free 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

• Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) or amyloidosis that can be attributed to the plasma cell proliferative disorder

• Clonal bone marrow plasma cells <10%

• Urinary monoclonal protein <500mg/24h

• 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 hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) or amyloidosis that can be attributed to the plasma cell proliferative disorder

Patients suspected to have a solitary plasmacytoma should have a PET scan performed to conclusively rule out other lesions, once the initial lesion is biopsied and confirmed to be plasmacytoma. The initial evaluation is similar to that for myeloma, including a bone marrow aspirate and biopsy. These patients are primarily treated with radiation therapy to the affected area, and surgery is reserved for specific situations such as those in case of bone lesions with extensive destruction that require stabilization or soft tissue masses with pressure symptoms. After completion of treatment, patients should be followed by regular monitoring of M-protein and imaging studies as indicated, given the risk of progression to MM. Older patients, bone plasmacytoma especially of the axial skeleton, persistent monoclonal protein after radiation therapy, presence of marrow involvement, increased angiogenesis in the plasmacytoma, and presence of circulating PCs, all suggest a higher risk of progression.

• 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 hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) or amyloidosis that can be attributed to the plasma cell proliferative disorder

• Polyneuropathy

• Monoclonal plasma cell proliferative disorder

• Any one of the 3 other major criteria: sclerotic bone lesions, Castleman’s disease, elevated levels of VEGFA

• Any one of the following 6 minor criteria:

• Organomegaly (splenomegaly, hepatomegaly, or lymphadenopathy)

• Extravascular volume overload (edema, pleurl effusion, or ascites)

• Endocrinopathy (adrenal, thyroid,pituitary, gonadal, parathyroid, pancreatic)

• Skin changes (hyperpigmentation, hypertrichosis, glomeruloid hemangiomata, plethora, acrocyanosis, flushing, white nails)

• Papilloedema

• Thrombocytosis/polycythemia

• Presence of an amyloid-related systemic syndrome (e.g., renal, liver, heart, gastrointestinal tract, or peripheral nerve involvement)

• Positive amyloid staining by Congo red in any tissue (e.g., fat aspirate, bone marrow, or organ biopsy)

• Evidence that amyloid is light-chain-related established by direct exmination of the amyloid using mass spectrometry-based proteomic analysis or immunoeletronmicroscopy

• Evidence of a monoclonal plasma cell proliferative disorder (serum monoclonal protein, abnormal free light chain ratio, or clonal plasma cells in the bone marrow)

• Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma AND
  One or more of the myeloma defining events (MDEs):
  1. Evidence of end organ damage attributable to the underlying plasma cell proliferative disorder, specifically:
     • Hypercalcemia: serum calcium > 1 mg/dL higher than the upper limit of normal or >11 mg/dL
     • Renal insufficiency: creatinine clearance <40 mL/min or serum creatinine > 2 mg/dL
     • Anemia: hemoglobin > 2 g/dL below the lower limit of normal or a hemoglobin < 10 g/dL
     • Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT)
  2. One or more of the biomarkers of malignancy
     
     • Clonal bone marrow plasma cell percentage ≥ 60%
     • Involved: uninvolved serum-free light chain (FLC) ratio ≥ 100 (involved free light chain level must be > 10 mg/dL)
     • >1 focal lesions on magnetic resonance imaging (MRI) studies