Whole body MRI in
asymp
yptomatic plasma cell disease
Jens Hillengass, MD
University Hospital,
Heidelberg, Germany
German Cancer Research Center (dkfz),
Heidelberg, Germany
Purpose
Analysis of the prognostic significance of the
presence and number of focal lesions in whole
body MRI of 250 patients with asymptomatic
myeloma, MGUS and solitary plasmacytoma
Patient characteristics
n = 250
MGUS
asymptomatic
Plasmacytoma
MM
n
84
149
17
sex
f = 46
f = 73
f = 4
m = 38
m = 76
m = 13
median age 58 [21-82]
58 [25-81]
57 [40-83]
Definition of the international myeloma working group, Br. J. Haematol. 2003
study design
· Retrospective analysis
· period of imag
pge acquisition:
11/2003 ­ 04/2008
· last information:
01/2009
· median time of
of follow
follow-up:
21 months
prognostic factors
factors tested in
multivariate analysis
Pt
Prognos i
tic factors for MGUS*
MGUS*
·
M-Protein type (IgG vs non-IgG)
·
M-Protein-Level (>/= 15g/l)
Prognostic factors for asymptomatic MM**
·
M-protein concentration (>/= 40g/l)
·
presence of IgA
pg
·
reduction of uninvolved immunoglobulins
·
presence of urinary Bence Jones Protein
·
plasma cell infiltration in bone marrow (>/=
(>/ 20%)
Prognostic factors for plasmacytoma***
·
persistence of M-protein after 1year
·
medullary location
*Rajkumar 2005 Blood, Kyle 2002 NEJM; **Weber DM 1997 Br J Haematol, Kyle
NEJM 2007, ***Dimopoulos JCO 1992, Mehan ASH 2008
Examination
· 2 similar
similar 1.5
1.5 T standard
standard MRI
MRI-tomographs with
body matrix coil
Body Matrix Coil
MRI-Protocol
·
T1
i
we h
g t
hted t b
ur o
i
sp n
h
ec o sequence in
coronal orientation of head, thorax and
abdomen, pelvis and legs
·
T2 weighted short-tau inversion recovery
(STIR) sequence in coronal orientation of
head, thorax and abdomen, pelvis and
proximal lower extremities
·
T2* weighted flash 2D sequence in sagittal
it
orient t
a i
tion f
o th
the wh l
o e
i
sp ne
Focal lesions
Image analysis
· 2 experienced radiologists in
consensus reading blinded
to patients diagnosis
· Quantification of focal
lesions with a minimum
diameter of 5 mm in axial
and extra-axial Skeleton
Skeleton
patients with focal lesions
Nb
Number f
o
hl
whole group
MGUS
tt
asymptoma i
tic
Plasmacytoma
patients with
MM
focal lesions
n = 250
n = 84
n = 149
n = 17
in whole body
65 [26%]
6 [7%]
42 [28%]
6 [35%]
MRI
(more than 1)
in axial skeleton
18 [7%]
4 [5%]
12 [8%]
2 [12%]
only
(altogether)
in extra-
extra axial
32 [13%]
2 [2%]
19 [13%]
11 [65%]
skeleton only
(altogether)
in both
15 [6%]
0 [0%]
11 [7%]
4 [23%]
compartt
tments
(altogether)
patients with focal lesions
Nb
Number f
o
hl
whole group
MGUS
tt
asymptoma i
tic
Plasmacytoma
patients with
MM
focal lesions
n = 250
n = 84
n = 149
n = 17
in whole body
65 [26%]
6 [7%]
42 [28%]
6 [35%]
MRI
(more than 1)
in axial skeleton
18 [7%]
4 [5%]
12 [8%]
2 [12%]
only
(altogether)
in extra-
extra axial
32 [13%]
2 [2%]
19 [13%]
11 [65%]
skeleton only
(altogether)
in both
15 [6%]
0 [0%]
11 [7%]
4 [23%]
compartt
tments
(altogether)
patients with focal lesions
Nb
Number f
o
hl
whole group
MGUS
tt
asymptoma i
tic
Plasmacytoma
patients with
MM
focal lesions
n = 250
n = 84
n = 149
n = 17
in whole body
65 [26%]
6 [7%]
42 [28%]
6 [35%]
MRI
(more than 1)
in axial skeleton
18 [7%]
4 [5%]
12 [8%]
2 [12%]
only
(altogether)
in extra-
extra axial
32 [13%]
2 [2%]
19 [13%]
11 [65%]
skeleton only
(altogether)
in both
15 [6%]
0 [0%]
11 [7%]
4 [23%]
compartt
tments
(altogether)
patients with focal lesions
Durie/ Salmon-
MGUS
asymptomatic Plasmacytoma
PLUS*
MM
n = 84
n = 149
n = 17
MGUS (0 lesions)
78
107
0
I (1-4 lesions)
6
37
13
II (5-20 lesions)
0
43
III (>20 lesions)
0
11
*Durie 2003 The Hematology Journal
Progression free survival
univariate analysis
· number of focal lesions
lesions ­ progression into
a higher Durie/ Salmon-stage of disease:
p < 0.001
· number of focal lesions
lesions ­ progression into
symptomatic disease:
p < 0.001
Presence of
of focal
focal lesions and progression into a
higher D/S-stage of disease
Presence of
of focal
focal lesions and progression into a
symptomatic stage of disease
Progression free survival
multivariate analysis
· for MGUS and solitary plasmacytoma no
multivariate analysis feasible because of the
small number of events
Progression free survival
multivariate analysis
for
o asy
asympto
pt m
o at
a ic
tc multiple
utpe mye
yeloma
· number of focal lesions
lesions ­ progression into
a higher D/S-stage of disease
p < 0.001
· number of focal lesions ­ progression into
symptomatic disease
p < 0.001
· the only other prognostic factor in our cohort:
Plasma
ll
ce
t
concen
t
ra i
tion in bone marrow:
p = 00
0. 2
02
Conclusions
· The presence and number of focal lesions in
whole body MRI is an adverse prognostic factor
for the
the progression of asymptomatic monoclonal
plasma cell disease
· We recommend whole body MRI for
for initial work
work-
up in asymptomatic multiple myeloma and
plasmacy
pytoma
Acknowledgements
University of Heidelberg
German Cancer Research Center (DKFZ)
Department of Hematology
Department of Radiology
­ H. Goldschmidt
­S. Delorme
­ K. Neben
­T. Baeuerle
­ S. Ayyaz
­C. Zechmann
­ A.D. Ho
Department of Radiology
Department of Biostatistics
­ K. Fechtner
­C. Heiss
­ M.A. Weber
­T. Hielscher
­ H.U. Kauczor
­A. Benner