A PETHEMA study of high-dose therapy/stem
cell s
upport
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 A
,
S
. ureda5
Sureda J
, d
. e
de l a
la R
ubia6
Rubia J
, .
Besalduch7, J. García-Laraña8 J.F. San Miguel2.
1H C
. línic
Clínic B
arcelona 2
Barcelona, H C
. línico
Clínico Salamanca 3
Salamanca, H 1
. 2
12 d
e
de
Octubre, 4H Universitario Canarias, 5H. Sant Pau, 6H. La Fe,
7H. Son Dureta, 8 H. Ramón y Cajal
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
( )
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
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
t o
to t he
the
EBMT criteria.
Statistical methods: Kaplan & Meier, log-rank test
SPANISH
SP
PETHEMA
/ G
EM
GEM 2000
-
TRIAL
VBMCP/VBAD
RESISTANT
RESIST
DISEASE
Bu/MEL-140 or
MEL-200 / ASCT
CVB/ASCT or
mini-allo
SPANISH
SP
TRIAL
PETHEMA
/ G
EM-
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 / A
SCT
ASCT
CVB/ASCT or
mini-allo
Response after first autologous
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 "
i
m
"
cro
· 3 patient refusal
· 2 insufficient CD34
Response Up
-grading w
ith
with S
econd
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 (
7%)
(7%)
1 (
11
(1 %)
1%)
Primary Refractor
y
y M
y yeloma
y
Overall Survival
1,2
1,1
1,0
N=81
0,9
Median: 3.7 yrs
i
n
g
v
iv 0,8
0,7
ion Sur
rt 0,6
ropo
P
0,5
l
a
t
i
ve
0,4
mu
Cu 0,3
0,2
0,1
0,0
0
1
2
3
4
5
6
7
8
Years
Overall S
urvival
Survival
No-change vs Progressive Disease
1,0
0,9
0,8
n
g
vi 0,7
r
vi
No-change
0,6
ion Su
rt
0,5
Propo
0,4
l
a
t
i
ve
mu 0,3
Cu
0,2
Progressi
d
ve i
disease
0,1
p=0.000001
0,0
0
1
2
3
4
5
6
7
8
Years
Progression-free Survival
No-change vs Progressive Disease
1,0
0,9
0,8
g
v
in
0,7
i
v
0,6
ion Surv
rt
0,5
r
opo
P
0,4
l
a
ti
ve
0,3
No-change
u
mu
C
0,2
0,1
Progressive disease
0,0
p=0.00001
-0,1
0
1
2
3
4
5
6
7
Ye ars
Overall Survival
Primary Refractory vs Chemosensitive Myeloma
1,0
0,9
0,8
g
in
iv 0,7
o
n Surv 0,6
Chemosensitive
0,5
r
o
p
o
r
t
i
o
P
0,4
Refractory
u
l
a
ti
ve
m 0,3
Cu
0,2
0,1
p=0.0001
0,0
0
2
4
6
8
10
12
14
Years
Overall Survival
Progressive disease vs No-change vs Chemosensitive
1,0
0,9
0,8
n
g
vi 0,7
u
r
vi
No Change
S
No
S
0,6
ion
rt
0,5
Chemosensitive
v
e Propo 0,4
l
a
t
i
v
mu 0,3
Cu
0,2
Progressive disease
0,1
0,0
0
2
4
6
8
10
12
14
Years
C
l
onc
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.