Clinical, genomic and imaging predictor of myeloma progression

Clinical, genomic and imaging predictor of
myeloma progression from asymptomatic
monoclonal gammopathies
(Blood. 2014;123(1):78-85)
CR 簡聖軒
VS 劉俊煌 教授
MGUS
Asymptomatic
MM
Symptomatic
MM
Extra
medullary
Clonal cells
PC > 10%
End organ damage
BM independent
MGUS
AMM
Serum M-protein <3.0 g/dL
+
Marrow plasma cells <10%
+
No related organ damage
No other B cell NHL or
amyloidosis
Serum M-protein ≥3.0 g/dL
and / or
Marrow plasma cells ≥10%
(clonal)
+
No related organ or tissue
impairment
C
R
A
B
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 612 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
Univariate analysis
Age ≧65
MRI focal lesion > 1
Hb <12 g/dL
GEP-70 risk score > -0.26
Albumin< 4 g/dL
B2M > 3 mg /L
GEP-70 PI > -2.73
Serum M ≧3 g/dL
Urine M > 0 g/dL
GEP poly-PC > 11.6
Low level of uninvolved Ig
A level of involved SFLC > 25 mg/dL
Elevated ratio of
involved/uninvolved SFLC > 10
Plasma > 20% in BM
Addition of GEP improved cumulative R2
by approximately 11 %
11%
Risk factor: SFLC >25 mg/dl
M spike > 3g/dL
GEP70 risk >-0.26
Risk factor: M spike > 3g/dL
BM PC > 20 %
Age ≧65
Risk factor: SFLC >25 mg/dl
M spike > 3g/dL
GEP70 risk >-0.26
Higher polytypic-PC risk score predicts reduced risk of
progression
Multivariate analysis
VS
Follow up time ?
First prospective
clinical trial
Mode for risk
identification
Genomic and
clinical based
Monitor and
intervention
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