A PETHEMA study of high-dose therapy/stem
cell support
support (HDT)
(HDT), including
including tandem
transplant, in primary refractory multiple
myeloma (MM):
(MM): identification
identification of
of two
two
populations with different outcome.
J. Bladé1, L. Rosiñol1, R. García-Sanz2, J.J. Lahuerta3, M.
Hernández-García4
-García , AS
A.
ureda5
Sureda , J. de
de la
la Rubia6
Rubia , J.
Besalduch7, J. García-Laraña8 J.F. San Miguel2.
1H. Clínic
Clínic Barcelona 2
Barcelona, H. Clínico
Clínico Salamanca 3
Salamanca, H1
H. 2
12 de
de
Octubre, 4H Universitario Canarias, 5H. Sant Pau, 6H. La Fe,
7H. Son Dureta, 8 H. Ramón y Cajal
Bk
Back
d
groun
It is generally assumed that patients with primary
refractory myeloma are the most likely to benefit from
early HDT/SCT.
In four reported series the CR rate was between 8
and 40% and the overall survival ranged from 4 to 6
years.
However, the outcome of patients with progessive
disease versus those with "no change" or "stable
disease" was not separately analyzed in published
series.
Background (II
g( )
HDT/SCT in Primary Refractory Myeloma
Patients
Age
B2M
CR
EFS
OS
Author, yr
(n)
(yrs)
mg/dL
(%)
(yrs)
(yrs)
Alexanian et al,
27
45
2.8
8
3.5
6
Blood, 1994
Vesole et al, Blood
72
50
-
15
1.7
4
1994
Singhal et al,
43
54
33
3.3
40
2
-
BMT, 2002
Kumar et al, BMT,
50
56
2.7
20
2.5
5
2004
Alexanian et al,
89
52
3.7
16
7*
7*
BMT 2004
* In patients achiving CR after HDT/SCT
Objective
To investigate the efficacy in terms of response
up-grading and survival of early HDT/SCT in
patients with primary refractory myeloma.
Patients and Methods
81 refractory patients (49 M, 32F, median age 56.5 yrs)
identified.
Response and progression defined according to
to the
the
EBMT criteria.
Statistical methods: Kaplan & Meier, log-rank test
SPANISH
SP
PETHEMA / GEM
GEM 2000
-
TRIAL
VBMCP/VBAD
RESISTANT
RESIST
DISEASE
Bu/MEL-140 or
MEL-200 / ASCT
CVB/ASCT or
mini-allo
SPANISH
SP
TRIAL PETHEMA / GEM-
GEM 2000
Primary Refractory patients
VBMCP/VBAD
50 stable disease
(62%)
81 refractory
31
3 pr
p ogr
og essiv
ess e
disease (38%)
Bu/MEL-140 or
MEL-200 / ASCT
ASCT
CVB/ASCT or
mini-allo
Response after first autologous
tl
transpl
t
an
Response
Overall
No
Progressive
(n=81)
change
disease
(n=50)
(n=31)
CR1 (IF-)
4 (5%)
1 (2%)
3 (10%)
Near-CR (EP-)
2 (2.5%)
1 (2%)
3 (10%)
PR
39 (48%)
()
24 (48%)
()
14 (45%)
()
MR
11 (13%)
9 (18%)
2 (6%)
No change
10 (%
(12 )
%)
10 (%
(20 )
%)
-
Progressive disease
8 (10%)
1 (2%)
7 (22.5%)
Early death (< 2 mos)
7 (8.6%)
3 (6%)
4 (13%)
Second High-dose Procedure
81 refractory patients
YES
NO
N=42 (52%)
N=39 (48%)
N=42
· 9 deaths
· 8 poor performance status
· 7 progressive disease
· 28 Autos
· 5 physician decision
· 11 "Allos": 1 allo-SP
· 4 CR after Tx1
9 "Minis"
· 4 unknown
1"
1 " i
m
"
cro
· 3 patient refusal
· 2 insufficient CD34
Response Up-grading with
with Second
Second HDT
"Auto" vs "Allo"
Auto
Allo
Response
(n=28)
(n=9)
CR1 (IF-
(
)
3 (10%)
()
3 (33%)
()
PR
3 (11%)
MR
5 (18%)
1 (11%)
No change
3 (10%)
1 (11%)
Progressive disease
4 (14%)
3 (33%)
Early deaths (< 2mos)
2(
2 7%)
(7%)
1(
1 11
(1 %)
1%)
Primary Refractory
yy Myeloma
y
Overall Survival
1,2
1,1
1,0
N=81
0,9
g
Median: 3.7 yrs
inivv 08
0,8
Sur 0,7
ionrt
0,6
ropoP 0,5
tivela 0,4
mu
Cu 0,3
0,2
0,1
00
0,0
012
345
67
8
Years
Overall Survival
Survival
No-change vs Progressive Disease
1,0
0,9
0,8
gnvi 0,7
rvi
No-change
Su 0,6
ionrt
0,5
Propo
0,4
tivela
mu 0,3
Cu
02
0,2
Pi
Progressive di
disease
0,1
p=0.000001
0,0
0
1
2
345
678
Years
Progression-free Survival
No-change vs Progressive Disease
1,0
0,9
0,8
ginv 07
0,7
iv
0,6
Surv
ionrt 0,5
ropo
P
0,4
vetila 0,3
No-change
muu 0,2
C
0,1
Progressive disease
0,0
p=0.00001
-0,1
0
1
2
3
45
67
Ye ars
Overall Survival
Primary Refractory vs Chemosensitive Myeloma
1,0
0,9
0,8
giniv 0,7
Survn 0,6
o
Chemosensitive
rtioop 0,5
ro
P
ve 0,4
tila
Refractory
um 0,3
Cu
0,2
01
0,1
p=0.0001
0,0
02
46
8
10
12
14
Years
Overall Survival
Progressive disease vs No-change vs Chemosensitive
1,0
0,9
0,8
gnvi 0,7
rviu
No Change
S
0,6
ionrt
0,5
Chemosensitive
Propoev 04
0,4
tivla
mu 0,3
Cu
0,2
Progressive disease
0,1
0,0
02
46
8
10
12
14
Years
Cl
Concl
i
us ons
Althought a high-dose therapy approach in patients
with primary refractory myeloma results in a high
overall response the CR rate is low.
Patients with progressive disease to the initial
chemotherapy have a short survival despite the
intensive approach.
Patients
with
"non-responding,
non-progressive
disease" have a similar survival than chemosensitive
patients.
Whether
the
good
outcome
of
this
population is mainly due to the effect of HDT or to the
natural history of a more indolent disease remains to
be determined.