Prognostic relevance of 18F-FDG PET/CT in newly
diagnosed multiple myeloma patients receiving up-
front autologous stem-cell transplantation:
a prospective study
Zamagni E.1, Nanni C.2, Patriarca F.3, Zannetti B.1,Pezzi A.1, Tacchetti P.1,
Englaro E.4,Perrone G.1,Buttignol S.3,BrioliA.1, Pantani L.1, Caroborante
F.3, Baccarani M.1, Fanti S.2,Cavo M1
1"Seragnoli" Institute of Hematology, University of Bologna
2 Institute of Nuclear Medicine, University of Bologna
3 Hematologic Clinic, University of Udine
4 Institute of Nuclear Medicine, University of Udine
Disclosures for Elena Zamagni
Research Support/P.I.
No relevant conflicts of interest to declare
Employee
No relevant conflicts of interest to declare
Consultant
No relevant conflicts of interest to declare
Major Stockholder
No relevant conflicts of interest to declare
Speakers Bureau
No relevant conflicts of interest to declare
Honoraria
No relevant conflicts of interest to declare
Scientific Advisory Board
No relevant conflicts of interest to declare
1
BACKGROUND
·18F-FDG PET/CT is a valuable method to carefully
monitor response and predict clinical outcomes in
various tumors, particularly lymphoma
·Incorporation of novel agents into ASCT affected
unprecedented rates of CR in young MM patients
·More sensitive techniques for detecting MRD after
ASCT are required
AIM OF THE STUDY
· To prospectively evaluate the prognostic significance of
FDG-PET/CT at diagnosis, after induction therapy and
after high dose therapy in patients with newly diagnosed
MM who received thalidomide incorporated into up-front
autologous stem cell transplantation (ASCT)
2
PATIENT POPULATION
· N° analyzed patients: 192
· Median follow-up: months 42
· Median follow-up of living patients: months 43
FDG-PET/CT STUDIES
· FDG-PET/CT performed:
· at baseline
· post induction therapy
· 3 months after ASCT
· every year during follow-up
· at relapse
· Bone marrow involvement: negative, diffuse,
number of focal lesions (> 0.5 cm)
·SUV value
· Presence of extramedullary disease
3
BASELINE PATIENT CHARACTERISTICS
N° patients
192
Median age (range)
56 (35-66)
% pts with creat >2
8
% pts with Ca > 10
9
ISS stage II-III (% pts)
45
% pts with del (13q)*
43
% pts with t(4;14)*
23
% pts with del(17p)*
15
ASCT
-single (% pts)
40
-double (%pts)
60
*80% pts screened for cytogenetic abnormalities (FISH) on CD 138+ bone marrow PC
BASELINE FDG-PET/CT CHARACTERISTICS
N° patients
192
Negative (% pts)
24
Positive (% pts)
76
1-3 focal lesions(% pts)
32
>3 FL or diffuse(% pts)
44
SUV(% pts)
low ( 4.2)
54
high (>4.2)
46
Extramedullary disease (% pts)*
6
*defined as presence of FDG-avid soft
tissue not contiguous to bone
4
CLINICAL OUTCOMES
TTP
PFS
1.00
1.00
0.80
0.80
0.60
58 months
0.60
56 months
0.40
0.40
0.20
0.20
0.00 0
12
24
36
48
60
72
84
96
108 120
0.00 0
12
24
36
48
60
72
84
96
108 120
months
months
OS
1.00
Best overall response:
0.80
88% at 4 yrs
VGPR rate 80%
0.60
CR rate 52%
0.40
0.20
0.00 0
12
24
36
48
60
72
84
96
108
120
months
TTP, PFS AND OS IN PATIENTS WITH
EXTRAMEDULLARY DISEASE
TTP
PFS
Extramedullary neg
Extramedullary neg
1.00
1.00
Extramedullary pos
Extramedullary pos
0.80
0.80
63% at 4 yrs
60% at 4 yrs
0.60
0.60
0.40
0.40
28% at 4 yrs
25% at 4 yrs
0.20
0.20
P= 0.0004
P= 0.0008
0.00 0
12
24
36
48
60
72
84
0.00 0
12
24
36
48
60
72
84
months
months
OS
1.00
89% at 4 yrs
0.80
65% at 4 yrs
0.60
0.40
Extramedullary neg
0.20
Extramedullary pos
P= 0.006
0.00 0
12
24
36
48
60
72
84
months
5
TTP AND PFS ACCORDING TO
BASELINE FDG-PET/CT:
NUMBER OF LESIONS
TTP
PFS
N° les 3
N° les 3
1.00
N° les > 3
1.00
N° les > 3
0.80
0.80
69% at 4 yrs
65% at 4 yrs
0.60
0.60
49% at 4 yrs
0.40
0.40
43% at 4 yrs
0.20
0.20
P= 0.006
P= 0.01
0.00 0
12
24
36
48
60
72
84
0.00 0
12
24
36
48
60
72
84
months
months
TTP, PFS AND OS ACCORDING TO BASELINE FDG-PET/CT:
SUV VALUE
TTP
PFS
TTP
1.00
1.00
0.80
0.80
66% at 4 yrs
64% at 4 yrs
0.60
0.60
SUV 4.2
SUV 4.2
54% at 4 yrs
43% at 4 yrs
0.40
SUV > 4.2
0.40
SUV > 4.2
0.20
0.20
P= 0.003
P= 0.008
0.00 0
12
24
36
48
60
72
84
0.00 0
12
24
36
48
60
72
84
months
months
OS
1.00
90% at 4 yrs
0.80
77% at 4 yrs
0.60
0.40
SUV 4.2
0.20
SUV > 4.2
P= 0.03
0.00 0
12
24
36
48
60
72
84
months
6
MULTIVARIATE ANALYSIS OF BASELINE
UNFAVORABLE PROGNOSTIC FACTORS
VARIABLES
HAZARD RATIO
P VALUE
(95% CI)
TTP
PET/CT > 4.2 SUV
2.37 (1.26-4.33)
0.007
Extramedullary disease
15. 43 (4.11-57.95)
0.000
del (17p) t(4;14)
1.86 (1.12-3.49)
0.05
PFS
PET/CT > 4.2 SUV
2.05 (1.13-3.72)
0.018
Extramedullary disease
15. 00 (4.03-55.88)
0.000
del (17p) t(4;14)
2.03 (1.10-3.72)
0.02
OS
Extramedullary disease
6. 99 (2.28-21.46)
0.001
del (17p) t(4;14)
2.36 (1.23-6.02)
0.05
POST INDUCTION FDG-PET/CT
CHARACTERISTICS
N° patients
85
Negative (%)
37
Positive (%)
63
-improved
14
-unchanged
43
-worstened
6
7
TTP, PFS AND OS ACCORDING TO POST-
INDUCTION FDG-PET/CT
TTP
PFS
1.00
1.00
0.80
0.80
69% at 4 yrs
71% at 4 yrs
0.60
0.60
44% at 4 yrs
40% at 4 yrs
0.40
0.40
SUV 4.2
SUV 4.2
0.20
0.20
SUV > 4.2
P= 0.003
SUV > 4.2
P= 0.004
0.00 0
12
24
36
48
60
72
84
96
108
120
0.00 0
12
24
36
48
60
72
84
96
108
120
months
months
OS
1.00
87% at 4 yrs
0.80
77% at 4 yrs
0.60
0.40
SUV 4.2
0.20
SUV > 4.2
P= 0.06
0.00 0
12
24
36
48
60
72
84
96
108
120
months
POST ASCT FDG-PET/CT
CHARACTERISTICS
N° patients
192
Negative (%)
65
Positive (%)
35
-improved
17
-unchanged
14
-worstened
4
Negative + VGPR (%)
95 P = 0.001
Positive + VGPR (%)
75
8
TTP, PFS AND OS ACCORDING TO
POST ASCT FDG-PET/CT
TTP
PFS
1.00
SUV 0
1.00
SUV 0
SUV > 0
SUV > 0
0.80
0.80
0.60
66% at 4 yrs
0.60
62% at 4 yrs
0.40
45% at 4 yrs
0.40
43% at 4 yrs
0.20
0.20
P= 0.01
P= 0.02
0.00 0
12
24
36
48
60
72
84
96 108 120
0.00 0
12
24
36
48
60
72
84
96
108 120
months
months
OS
1.00
88% at 4 yrs
0.80
0.60
75% at 4 yrs
0.40
SUV 0
0.20
SUV > 0
P= 0.02
0.00 0
12
24
36
48
60
72
84
96
108
120
months
OS ACCORDING TO FDG-PET/CT
IMAGING AT RELAPSE
OS
Post relapse OS
PET neg
1.00
1.00
PET pos
92% at 4 yrs
0.80
0.80
0.60
68% at 4 yrs
0.60
45 months
0.40
0.40
PET neg
26 months
0.20
PET pos
0.20
P= 0.03
P= 0.02
0.00 0
12
24
36
48
60
72
84
96
108
120
0.00 0
12
24
36
48
60
72
months
months
9
MULTIVARIATE ANALYSIS OF BASELINE LABORATORY AND
POST TREATMENT UNFAVORABLE PROGNOSTIC FACTORS
VARIABLES
HAZARD RATIO
P VALUE
(95% CI)
TTP
Not complete FDG PET suppression
2.12 (1.19-3.77)
0.01
Extramedullary disease
15. 43 (4.11-57.95)
0.000
del (17p) t(4;14)
1.86 (1.12-3.49)
0.05
< VGPR
2.10 (1.13-3.88)
0.017
PFS
Not complete FDG PET suppression
2.12 (1.19-3.77)
0.023
Extramedullary disease
5. 47 (1.89-15.81)
0.002
del (17p) t(4;14)
1.92 (1.09-3.39)
0.025
< VGPR
2.11 (1.16-3.83)
0.013
OS
Not complete FDG PET suppression
3.57 (1.03-12.39)
0.04
Relapse
9.56 (2.85-32.05)
0.000
CONCLUSION
·Independent impact of FDG-PET/CT at diagnosis on
clinical outcomes (TTP, PFS and OS)
·number of focal lesions
· intensity of tumor metabolism (SUV)
·EMD
·Persistence of high tumor metabolism (SUV) by FDG-
PET/CT after induction therapy predicted worst
outcome (TTP, PFS and OS)
10
CONCLUSION
·FDG-PET/CT after ASCT is a reliable tool to predict
prognosis and identify patients at different risk of
progression.
·Complete FDG suppression after ASCT was associated
with extended PFS and OS both in univariate and
multivariate analysis
·FDG-PET/CT involvement at the time of relapse was
associated with shortened survival after relapse
CONCLUSION
·Based on these data and additional data from other
groups, aims to evaluate MRD after ASCT should include
also imaging techniques such as FDG-PET/CT and/or
whole body MRI
11
ACKNOWLEDGMENTS
Myeloma Research Unit
Nuclear Medicine
Michele Cavo
Cristina Nanni
Elena Zamagni
Emanuela Englaro
Beatrice Zannetti
Stefano Fanti
Francesca Patriarca
Paolo Castellucci
Silvia Buttignol
Paola Tacchetti
Giulia Perrone
Annamaria Brioli
Lucia Pantani
Statistical Analysis
Francesca Caroborante
Annalisa Pezzi
Mauro Fiacchini
Katia Vitali
12