Clinical, genomic and imaging predictor of myeloma progression from asymptomatic monoclonal gammopathies

CR簡聖軒VS劉俊煌教授

(Blood. 2014;123(1):78-85)

MGUSAsymptomatic

MM

Symptomatic

MM

Extra

medullary

Clonal cells

PC > 10%

End organ damage

BM independent

AMM

Serum M-protein ≥3.0 g/dLand / or

Marrow plasma cells ≥10% (clonal)

+No related organ or tissue

impairment

MGUS

Serum M-protein

Observe !

PC > 10 %, M> 3g/dL

PC > 10 %, M< 3g/dL

PC < 10 %, M< 3g/dL

N Engl J Med 2007;356:2582-90

51 gene Up regulation

19 gene down regulation

EFS OS

Prospective observation trail : SWOG S0120

MGUS, SMM, solitary plasmacytoma

Hemogram, serum/urinary M protein, SEP, IEP, B2M, free light chain, metaphase karyotyping, MRI

At 3,6 and 12 months at first year, then every 6-12 months

Collected to isolate CD 138+ plasma cell with immunomagnetic bead selection

Monitored by flow cytomerty for > 85%

Affymetrix U133 plus 2.0 microarrays, generate risk score based on a validated 70-gene model (GEP-70)

GEP -70score

Age ≧65

Low level of uninvolved Ig

Urine M > 0 g/dL

Serum M ≧3 g/dL

B2M > 3 mg /L

Albumin< 4 g/dL

Hb 25 mg/dL

Elevated ratio of involved/uninvolved SFLC > 10

Plasma > 20% in BM

GEP-70 risk score > -0.26

GEP-70 PI > -2.73

MRI focal lesion > 1

Univariate analysis

GEP poly-PC > 11.6

Addition of GEP improved cumulative R2

by approximately 11 %

11%

Risk factor: SFLC >25 mg/dlM spike > 3g/dLGEP70 risk >-0.26

Risk factor: M spike > 3g/dLBM PC > 20 % Age ≧65

Risk factor: SFLC >25 mg/dlM spike > 3g/dLGEP70 risk >-0.26

Higher polytypic-PC risk score predicts reduced risk of

progression

Multivariate analysis

Follow up time ?

VS

First prospective clinical trial

Mode for risk identification

Genomic and clinical based

Monitor and intervention

M

M

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