SHOULD CR
ACHIEVEMENT BE
A MAJOR
TREATMENT
OBJECTIVE?
NO
Kos June, 2007
Mario Boccadoro
DIVISIONE UNIVERSITARIA DI EMATO
EMATOLOGIA
OGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Response rate and survival
in MM: conventional chemotherapy
N f patients
N.of
ti t
Blade J et al.
243
BJH 1994
Oivanen TM et al. 432
R
Response
Median Survival
(months)
At least PR
43.4
CR
42
No Response
19
> PR
< 70 ys v >70
59 v 44
PR
< 70 ys v >70
59 v 40
EJH 1999
Durie BMG et al.
1555
Response
35 v 34
JCO 2004
N R
No
Response
30
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Survival by response categories
Durie BMG et al. JCO 2004
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Survival by disease progression
Durie BMG et al. JCO 2004
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Response rate and survival in MM:
conventional chemotherapy versus highdose chemotherapy
N.of patients
F
Fermand
d JP ett al.
l
Response
(% CR)
Median Survival
(months)
CC
HDT
CC
HDT
190
20
36
47 6
47.6
47 8
47.8
216
11
30
61
66
JCO 2005
Blade’ J et al
Blade
al.
Blood 2005
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Survival by therapy
Fermand JP et al. JCO 2005
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Survival by therapy
Blade’ J et al. Blood 2005
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Response rate and survival in MM:
high-dose chemotherapy
N.of patients
126
Response
(%)
PFS
OS
(months)
(months)
CR
33
15
25
No CR
67
11
24
Rajkumar SV et al.
BMT 2000
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
OS and PFS by CR
Rajkumar
j
SV et al.
BMT 2000
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Response rate and survival in MM:
New Drugs
Thalidomide
No Thalidomide
345
323
CR (%)
62
43
5 year-EFS (%)
56
44
5 year
year-OS
OS (%)
65
65
N. of patients
Barlogie B et al.
NEJM 2006
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
SHOULD CR ACHIEVEMENT BE A
MAJOR TREATMENT OBJECTIVE?
NO
N relationship
No
l ti
hi between
b t
CR and
d survival
i l
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
SHOULD CR ACHIEVEMENT BE A
MAJOR TREATMENT OBJECTIVE?
NO
CR
CURE
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
SHOULD CR ACHIEVEMENT BE A
MAJOR TREATMENT OBJECTIVE?
NOÆ WHY ???
CR
CURE
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
SHOULD CR ACHIEVEMENT BE A
MAJOR TREATMENT OBJECTIVE?
NOÆ WHY ???
• Cosmetic effect
• Malignant characteristics of the neoplastic cells
• Benign characteristics of the neoplastic cells
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
MP vs Dexamethasone-Based Regimens
((IFM 95-01 Trial))
•
•
•
488 patients aged 65-75 yr randomized to MP, MD, D, or D-IFNα
(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-IFNα
n
109
110
109
101
≥PR↓ (P<0.001)
51%
74%
40%
42%
CR (P=NS)
1%
3%
1%
1%
EFS (mo)
21 1 ± 1.7
21.1
17
22 9 ± 2.0
22.9
20
12 2 ± 1.0
12.2
1 0*
15 2 ± 2.7
15.2
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
Facon T et al. Blood. 2006; 107:1292
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
SHOULD CR ACHIEVEMENT BE A
MAJOR TREATMENT OBJECTIVE?
NOÆ WHY ???
• Cosmetic effect
• Malignant characteristics of the neoplastic cells
• Benign characteristics of the neoplastic cells
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
High serum free-light chain levels and their rapid reduction in
response to therapy define an aggressive multiple myeloma
subtype with poor prognosis
prognosis.
SFLC baseline levels >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 UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Early responder myeloma: kinetic studies identify
ap
patient subgroup
g p characterized by
y very
yp
poor p
prognosis.
g
J Clin Oncol 1989
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Early responder myeloma: kinetic studies identify
a patient subgroup characterized by very poor prognosis
prognosis.
J Clin Oncol 1989
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
SHOULD CR ACHIEVEMENT BE A
MAJOR TREATMENT OBJECTIVE?
NOÆ WHY ???
• Cosmetic effect
• Malignant characteristics of the neoplastic cells
• Benign characteristics of the neoplastic cells
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Complete response in myeloma extends survival without, but not
with history of prior monoclonal gammopathy of undetermined
significance or smouldering disease
disease.
Previous MGUS, SMM, or SPC
56/688 CR 22% vs 48%
Survival similar
M Pineda-Roman Brit J of Haemat 136 (3), 393–399.
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
Gene-expression
G
i signature
i
t
off benign
b i monoclonal
l
l gammopathy
th
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
th 10 years after
ft autotransplantation.
t t
l t ti
Zhan F Blood 2007
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY
SHOULD CR ACHIEVEMENT BE A
MAJOR TREATMENT OBJECTIVE?
YES but …..
YES,
• Cosmetic effect
• Malignant characteristics of the neoplastic cells
• Benign characteristics of the neoplastic cells
NEW DRUG ???
DIVISIONE UNIVERSITARIA DI EMATOLOGIA
AZIENDA OSPEDALIERA SAN GIOVANNI
TORINO, ITALY