Conventionally-Defined and PET/CT-Defined Complete
Response
(CR)
to
Novel
Agent-Based
Induction
Therapy and Autologous Stem-Cell Transplantation
(ASCT) In Multiple Myeloma (MM): A Prospective Study
of Clinical and Prognostic Implications
Zamagni E.1, Nanni C.2,Patriarca F.3, Tacchetti P.1, Englaro E.4, Perrone
G.1,Buttignol S.3,BrioliA.1, Pantani L.1, Zannetti B.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
In compliance with ACCME policy, ASH requires the following disclosures to the session audience:
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
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Honoraria
No relevant conflicts of interest to declare
Scientific Advisory Board
No relevant conflicts of interest to declare
Presentation includes discussion of the following off-label use of a drug or medical device: N/A
1
AIM OF THE STUDY
· To prospectively evaluate the prognostic significance and
the clinical implications of FDG-PET/CT after induction and
high-dose therapy in patients with newly diagnosed MM
who received thalidomide incorporated into up-front
autologous stem cell transplantation (ASCT)
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
· Presence of extramedullary disease
2
BASELINE PATIENT CHARACTERISTICS
PET-studied
Whole patient
P value
patients
population
N° patients
192
378
Median age (range)
57 (32-82)
57 (35-66)
NS
Median creatinine (range) (mg/dl)
1.1 (0.5-9.9)
1.0 (0.3-10.9)
NS
% patients with 2 mg/dl
8
10
Median calcium (range) (mg/dl)
9.1 (2.9-15.7)
9.3 (5-13.9)
NS
% patients with serum Ca > 10 mg/dL
14
12
% patients with ISS stage II-III
47
50
NS
% patients with del (13q)
43
45
NS
% patients with del (17p)
15
6
0.000
% patients with t (4;14)
23
14
0.01
Median CRP (mg/L)
4 (0-39)
3.7(0-29)
NS
Median LDH (UI/L)
295 (103-2325)
305(102-1996)
NS
ASCT:
single (% patients)
35
48
0.003
double (% patients)
65
52
Best response to ASCT(s) CR/VGPR (%)
52/80
34/61
0.000
Median PFS (months)
56
46
0.001
4-year estimated OS
88
70
0.000
Median follow-up: 42 months PET studied pts, 65 months whole population
Zamagni E. et al, Blood 2011, 118: 5989-5995
BASELINE FDG-PET/CT CHARACTERISTICS
N° patients
192
% Patients with negative PET/CT
24
% Patients with positive PET/CT
76
1-3 FLs
32
>3 FLs
27
diffuse
17
% Patients with lower SUV ( 4.2)
54
% Patients with high SUV (> 4.2)
46
% Patients with EMD
6
% 1-3 FLs
25
% >3FLs
59
% diffuse
16
% SUV 4.2
38
% SUV > 4.2
62
Zamagni E. et al, Blood 2011, 118: 5989-5995
3
POST-INDUCTION FDG-PET/CT
CHARACTERISTICS
N° patients
85
Negative (%)
37
Positive (%)
63
-improved
14
-unchanged
43
-worstened
6
Median SUVmax value (range)
2,4 (0-17,9)
Mean SUVmax value (SD)
3,0 (3,5)
TTP, PFS AND OS ACCORDING TO
POST-INDUCTION FDG-PET/CT
TTP
PFS
1.00
1.00
69% at 4 yrs
69% at 4 yrs
0.75
0.75
0.50
0.50
44% at 4 yrs
44% at 4 yrs
0.25
0.25
SUV 4.2
SUV
SUV 4.2
4.2
P= 0.007
SUV > 4.2
P= 0.007
SUV
SUV > > 4.2
4.2
0.00
0.00
0
12
24
36
48
60
0
12
24
36
48
60
months
months
OS
1.00
88% at 4 yrs
0.75
0.50
75% at 4 yrs
0.25
SUV 4.2
P= 0.07
SUV > 4.2
0.00
0
12
24
36
48
60
months
Zamagni E. et al, Blood 2011, 118: 5989-5995
4
PFS ACCORDING TO SUV MODIFICATION
POST-INDUCTION
1.00
SUV basal >4.2, post-ind.< 4.2
SUV basal >4.2, post-ind. > 4.2
0.75
63% at 4 yrs
0.50
42% at 4 yrs
0.25
P= 0.049
0.00
0
6
12
18
24
30
36
42
48
54
60
months
CORRELATION BETWEEN CONVENTIONALLY-DEFINED
RESPONSE AND SUVmax POST-INDUCTION
20
15
10
5
0
CR+nCR
VGPR+PR
SD
PROG
Cuzick's trend test P= 0,008
5
RESPONSE BY PET/CT AFTER INDUCTION IS AN
EARLY PREDICTOR FOR ATTAINMENT OF
AT LEAST VGPR AFTER ASCT
Post-ASCT
Post-induction PET/CT
response
SUV < 4.2
SUV 4.2
< VGPR
6%
25%
VGPR
94%
75%
P = 0.04
POST-ASCT FDG-PET/CT
CHARACTERISTICS
N° patients
192
Negative (%)
65
Positive (%)
35
-improved
17
-unchanged
14
-worstened
4
Median SUVmax value (range)
0 (0-24)
Mean SUVmax value (SD)
1,23 (2,56)
Negative + VGPR (%)
94
P = 0.003
Positive + VGPR (%)
75
6
CORRELATION BETWEEN CONVENTIONALLY-DEFINED
RESPONSE AND SUVmax POST-ASCT
25
20
15
10
5
0
CR+nCR
VGPR
PR+SD
Cuzick's trend test P= 0,001
TTP, PFS AND OS ACCORDING TO
POST-ASCT FDG-PET/CT
TTP
PFS
1.00
SUV 100% reduction
1.00
SUV 100% reduction
SUV < 100% reduction
SUV < 100% reduction
0.75
0.75
49% at 4 yrs
47% at 4 yrs
0.50
0.50
0.25
32% at 4 yrs
0.25
32% at 4 yrs
P= 0.01
P= 0.02
0.00
0.00
0
12
24
36
48
60
0
12
24
36
48
60
months
months
OS
1.00
79% at 4 yrs
0.75
Complete FDG-PET/CT suppression
66% at 4 yrs
on multivariate analysis:
0.50
-PFS: HR 0,53 (0,30-0,94), P=0,03
0.25
SUV 100% reduction
P= 0.02
-OS: HR 0,26 ( 0,07-0,89), P=0,03
SUV < 100% reduction
0.00
0
12
24
36
48
60
months
Zamagni E. et al, Blood 2011, 118: 5989-5995
7
CORRELATION BETWEEN TTP AND SUVmax POST-ASCT
60
54
48
42
36
30
months 24
18
12
6
0
Pet suv <4.2
Pet suv 4.2-6
Pet suv 6+
Correlation coefficient = -0,67, P= 0,008
Cuzick's trend test P= 0,017
All the patients with post-ASCT SUVmax 4,2 subsequently relapsed
PFS ACCORDING TO SUV MODIFICATION
POST-ASCT
1.00
SUV basal >4,2, final < 4.2
SUV basal >4,2, final > 4.2
0.75
45% at 4 yrs
0.50
21% at 4 yrs
0.25
P= 0.04
0.00
0
6
12
18
24
30
36
42
48
54
60
months
8
PFS ACCORDING TO POST-ASCT PET/CT IN
PATIENTS ACHIEVING CR
CONCLUSION
·Persistence of high tumor metabolism after induction
therapy predicted worst outcome (TTP, PFS and OS)
·A strong correlation between «conventionally defined»
response and SUV max reduction was evident
·SUV max reduction after induction therapy was linked with
the risk of progression
·PET/CT response after induction was an early predictor of
conventionally defined high quality response post-ASCT
9
CONCLUSION
·Complete FDG suppression after ASCT correlated with
clinical outcomes in terms of reduced risk of progression
and death
·SUVmax after ASCT correlated with the risk of disease
recurrence and could identify different groups of patients at
different risk of progression
·PET/CT retained prognostic relevance also in patients
achieving conventionally defined CR: going through a
«deepest level of CR»
CONCLUSION
·Serial evaluation with PET/CT scans after induction
treatment and after ASCT could contribute to the design of
individualized patients therapies
·Integrating PET/CT scanning into the algorithm of MM
follow-up may improve disease management
10
OPEN ISSUES
·To define standardized criteria for PET/CT imaging
definitions, PET positivity and semi-quantitative SUV
evaluations
·To define the best timing of PET/CT evaluations
ACKNOWLEDGMENTS
Myeloma Research Units
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
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