Anzeige
Erschienen in:
04.04.2019 | Guide Line
JSH practical guidelines for hematological malignancies, 2018: III. Myeloma-1. Multiple myeloma (MM)
Erschienen in: International Journal of Hematology | Ausgabe 5/2019
Einloggen, um Zugang zu erhaltenExcerpt
Multiple myeloma (MM) is a disease characterized by monoclonal (neoplastic) proliferation of plasma cells and increased levels of the plasma cell product monoclonal immunoglobulin (M-protein) in serum and urine [1]. In Japan, its incidence is approximately 5 per 100,000 population and it causes approximately 4000 deaths per year. It accounts for approximately 1% of all malignancies and approximately 10% of all hematopoietic tumors, and its incidence and mortality rate are increasing every year. Criteria by the International Myeloma Working Group (IMWG) are widely used in its diagnosis (Table 1) [2, 3].
Table 1 IMWG criteria for the diagnosis of plasma cell neoplasms
|
Non-IgM monoclonal gammopathy of undetermined significance (MGUS)
|
(1) Serum non-IgM M-protein < 3 g/dL
(2) Clonal bone marrow plasma cells < 10%
(3) Absence of end-organ damage (CRAB or amyloidosis)
Meets all the criteria in (1) through (3)
|
|
IgM monoclonal gammopathy of undetermined significance (MGUS)
|
(1) Serum IgM M-protein < 3 g/dL
(2) Lymphoplasmacytic infiltrate in bone marrow < 10%
(3) No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, hepatosplenomegaly, or other end-organ damage
Meets all of the criteria in (1) through (3)
|
|
Light-chain monoclonal gammopathy of undetermined significance (MGUS)
|
(1) Abnormal serum free light chain ratio (< 0.26 or > 1.65)
(2) Increased serum level of the appropriate free light chain
(3) No heavy chain expression on immunofixation
(4) Absence of end-organ damage (CRAB or amyloidosis)
(5) Clonal bone marrow plasma cells < 10%
(6) Urinary M-protein < 500 mg/24 h
Meets all the criteria in (1) through (6)
|
|
Solitary plasmacytoma of bone/of soft tissue
|
(1) Biopsy-proven plasmacytoma of bone or soft tissue with evidence of clonal plasma cells
(2) Normal bone marrow with no evidence of clonal plasma cells
(3) Normal bone X-ray and MRI (or CT) of spine and pelvis (except for the solitary plasmacytoma lesion)
(4) Absence of end-organ damage (CRAB)
Meets all of the criteria in (1) through (4)
|
|
Solitary plasmacytoma with minimal marrow involvement of bone/of soft tissue
|
(1) Biopsy-proven plasmacytoma of bone or soft tissue with evidence of clonal plasma cells
(2) Clonal bone marrow plasma cells < 10%
(3) Normal bone X-ray and MRI (or CT) of spine and pelvis (except for the solitary plasmacytoma lesion)
(4) Absence of end-organ damage (CRAB)
Meets all of the criteria in (1) through (4)
|
|
Smoldering (asymptomatic) multiple myeloma
|
(1) Serum M-protein (IgG or IgA) ≥ 3 g/dL or urinary M-protein ≥ 500 mg/24 h
(2) Clonal bone marrow plasma cells ≥ 10% but < 60%
(3) Absence of myeloma-defining events (MDE)* or amyloidosis
Meets either (1) or (2), plus (3)
|
|
(Symptomatic) multiple myeloma secretory/non-secretory
|
(1) Clonal bone marrow plasma cells ≥ 10% or biopsy-proven plasmacytoma of bone or soft tissue
(2) One or more MDE*, or meets one or more biomarker** criteria
Meets (1) and (2)
If bone marrow plasma cells in (1) are < 10%, bone lesions must be detected at 2 or more sites
|
|
Multiple solitary plasmacytoma
|
(1) Serum or urinary M-protein not detected or only detected in trace amounts
(2) Plasmacytoma of clonal plasma cells or bone destruction at two or more sites
(3) Normal bone marrow
(4) Normal skeletal findings (except for plasmacytoma lesion)
(5) Absence of end-organ damage (CRAB)
Meets all the criteria in (1) through (5)
|
|
Plasma cell leukemia
|
(1) Peripheral blood plasma cells > 2000/μL
(2) Plasma cell fraction ≥ 20% of white blood cells
Meets (1) and (2)
|
|
POEMS syndrome
|
See section on POEMS syndrome
|
|
Systemic AL amyloidosis
|
See section on systemic AL amyloidosis
|
|
Myeloma-defining events (MDE)*
|
Following types of end-organ damage caused by the plasma cell neoplasm:
|
|
Hypercalcemia: Increase in serum Ca to > 11 mg/dL or more than 1 mg/dL above upper limit of normal
|
|
|
Renal failure: CrCl < 40 mL/min or serum Cr > 2.0 mg/dL
|
|
|
Anemia: Decrease in hemoglobin to < 10 g/dL or more than 2 g/dL below lower limit of normal
|
|
|
Bone lesions: One or more lesions detected on bone X-ray, CT, or PET-CT
|
|
|
Myeloma-defining biomarkers**
|
Has one or more of the following biomarkers**:
(1) Clonal bone marrow plasma cells ≥ 60%
(2) Involved/uninvolved free light chain (serum FLC) ratio ≥ 100 (involved FLC must be ≥ 100 mg/L)
(3) Focal bone lesions of ≥ 5 mm at 2 or more sites on MRI
|
Table 2 List of tests performed before treatment
|
General tests
Urinalysis, fecal hemoglobin, complete blood count/morphology, coagulation test, biochemical/immunological tests (total protein, albumin, total bilirubin, AST, ALT, ALP, LDH, amylase, ammonia, uric acid, blood glucose, BUN, creatinine, sodium, potassium, calcium, protein fractions, beta-2 microglobulin, CRP), HBs antigen, HBc antibody, HBs antibody, HCV antibody, HIV antibody, chest X-ray, ECG, arterial oxygen saturation
|
|
Detection and quantitation of M-protein
Protein fractions (serum and urine), quantitative 24-h urine protein
Immunoelectrophoresis (serum and urine) or immunofixation
Immunoglobulin assays (IgG, IgA, IgD, IgM, IgE)
Quantitative serum free light chain and kappa/lambda ratio
|
|
Increase in bone marrow plasma cells and verification of plasmacytoma
Bone marrow aspiration/biopsy
Surface phenotypic analysis by flow cytometry
Chromosome analysis and FISH
|
|
Evaluation of end-organ damage
Skeletal survey (skull: frontal/lateral, cervical/thoracic/lumbar spine: frontal/lateral, ribs: frontal, pelvis: frontal, left/right humerus: frontal, left/right antebrachial bones: frontal, left/right femur: frontal, left/right lower leg bones: frontal)
Plain CT (neck, chest, abdomen, and pelvis)
Spinal and iliac MRI
FDG-PET
Bone turnover markers (urinary deoxypyridinoline, serum NTx, urinary CTx, bone-specific alkaline phosphatase, and osteocalcin) (Note: May not be covered by Japanese National Health Insurance)
Creatinine clearance
Echocardiogram
|
|
Other tests (added as necessary)
Biopsy (subcutaneous tissue, bone marrow, lips, stomach, or kidneys), blood/plasma/serum viscosity, funduscopy, thymidine kinase, cryoglobulin
|
Table 3 International staging system (ISS)
|
Stage
|
Criteria
|
Median survival time
|
|---|---|---|
|
I
|
Serum beta-2 microglobulin < 3.5 mg/L
Serum albumin ≥ 3.5 g/dL
|
62 months
|
|
II
|
Not stage I or III
|
44 months
|
|
III
|
Serum beta-2 microglobulin ≥ 5.5 mg/L
|
29 months
|