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SHOULD CR
ACHIEVEMENT BE
A MAJOR
TREATMENT
OBJECTIVE?
NO
Kos June, 2007
Mario Boccadoro
DIVISIONE UNIVERSITARIA
UNIVERSIT
DI
DI EMA
E
T
MA
EMA O
T
OGIA
L
AZIENDA OSPEDALIERA SAN GIOVANNI
GIOV
TO
T RINO,
O
ITAL
IT
Y
AL

Response rate and survival
in MM: conventional chemotherapy
chemotherapy
Nf
N.of pati
ti
t
en s
Response
Median Survival
(months)
Blade J et al.
243
At least PR
43.4
BJH 1994
CR
42
No Response
19
Oivanen TM et al. 432
> PR
< 70 ys v >70
59 v 44
EJH 1999
PR
< 70 ys v >70
59 v 40
Durie BMG et al.
1555
Response
35 v 34
JCO 2004
NR
No Response
30
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Survival by response categories
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
Durie BMG et al. JCO 2004
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Survival by disease progression
Durie BMG et al. JCO 2004
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Response rate and survival in MM:
conventional chemotherapy versus high-
dose chemotherapy
N.of patients
Response
Median Survival
(% CR)
(months)
CC
HDT
CC
HDT
Fd
Fermand JP
JP et al.
190
20
36
47 6
.
47 8
.
JCO 2005
Blade' Je
J ta
et l
al.
216
11
30
61
66
Blood 2005
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Survival by therapy
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
Fermand JP et al. JCO 2005
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Survival by therapy
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
Blade' J et al. Blood 2005
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Response rate and survival in MM:
high-
high dose chemotherapy
N.of patients
Response
PFS
OS
(%)
(months)
(months)
126
CR
33
15
25
No CR
67
11
24
Rajkumar SV et al.
BMT 2000
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

OS and PFS by CR
Rajkumar SV et al.
BMT 2000
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Response rate and survival in MM:
New Drugs
Thalidomide
No Thalidomide
N. of patients
345
323
CR (%)
62
43
5 year-EFS (%)
56
44
5 year-OS (%)
65
65
Barlogie B et al.
NEJM 2006
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

SHOULD CR ACHIEVEMENT BE A
MAJOR TREAT
TREA MENT
TMENT OBJECTIVE?
NO
Nl
No rel t
a i
ti
h
ons i
hip b t
e ween CR
CR
d
an
i
surv
l
va
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

SHOULD CR ACHIEVEMENT BE A
MAJOR TREAT
TREA MENT
TMENT OBJECTIVE?
NO
CR
CURE
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

SHOULD CR ACHIEVEMENT BE A
MAJOR TREAT
TREA MENT
TMENT OBJECTIVE?
NO
WHY ???
CR
CURE
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

SHOULD CR ACHIEVEMENT BE A
MAJOR TREAT
TREA MENT
TMENT OBJECTIVE?
NO
WHY ???
· Cosmetic effect
· Malignant characteristics
characteristics of
of the
the neoplastic cells
cells
· Benign characteristics of the neoplastic cells
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

MP vs Dexamethasone-Based Regimens
(IFM
(
95-01 Trial)
·
488 patients aged 65-75 yr randomized to MP, MD, D, or D-IFN
(12 courses at 6-wk intervals)
·
FU 82.8 mo, OS 35.0 mo (415/488), EFS 18.3 mo (473/488) for
whole series
·
Standard MP gold standard for treatment of older pts
Regimen
MP
MD
D
D-IFN
n
109
110
11
109
101
PR (P<0.001)
51%
74%
40%
42%
CR (P=NS)
1%
3%
1%
1%
EFS (mo)
(mo)
21 1
. ± 17
1.7
22 9
. ± 20
2.0
12 2
. ± 10
1. *
0
15 2
. ± 27
2. *
7
OS (mo)
34.0 ± 3.6
39,6 ± 3.1
33.4 ± 2.0
32.0 ± 5.3
*P<0.001 for pts not receiving Melphalan
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
Facon T et al. Blood. 2006; 107:1292
TORINO, ITAL
A Y

High serum free-light chain levels and their rapid reduction in
response to therapy define an aggressive multiple myeloma
subtype with poor prognosis.
SFLC baseline levels
levels >75mg/dL
>75mg/dL
33%
301
CR
37
20
p<0.002
EFS
73
90
p<0.001
OS
76
91
p<0.001
Van Rhee F, Blood 2007
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Early responder myeloma: kinetic studies identify
a patient subgrou
pg
p characterized by very poor
p
pro
p gnosis.
g
J Clin Oncol 1989
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Early responder myeloma: kinetic studies identify
a patient subgroup characterized by
by very
very poor prognosis.
J Clin Oncol 1989
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Complete response in myeloma extends survival without, but not
with history of prior monoclonal gammopathy of undetermined
significance or
or smouldering
smouldering disease.
Previous MGUS, SMM, or SPC
56/688 CR 22% vs 48%
Survival similar
M Pineda-Roman Brit J of Haemat 136 (3), 393399.
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

Gene-expressii
ion si
t
gna ure f
o b
i
en gn monocl
l
ona
t
gammopa h
thy
evident in multiple myeloma is linked to good prognosis.
The MGUS-L signature was also seen in plasma cells from
15 of 20 patients surviving
more than 10 years after autotransplantation.
Zhan F Blood 2007
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y

SHOULD CR ACHIEVEMENT BE A
MAJOR TREAT
TREA MENT
TMENT OBJECTIVE?
YES, but .....
· Cosmetic effect
· Malignant characteristics
characteristics of
of the
the neoplastic cells
cells
· Benign characteristics of the neoplastic cells
NEW DRUG ???
DIVISIONE UNIVERSITARI
A A DI EMAT
A OLOGIA
I
AZ
A IENDA OSPEDAL
A IERA SAN
A GIO
I VA
V NNI
A
TORINO, ITAL
A Y