Feasibility and efficacy of a planned
second transplant intensification ("Auto"
or "Mini-allo") in patients with MM not
achieving CR or near-CR with a first
autologous intensification.
Results from a Spanish PETHEMA/GEM
study.
L.Rosiñol, J.J.Lahuerta, A. Sureda, J. de la Rubia, J.
García Laraña , M. Hernández García, B. Hernández
Ruíz, J.A. Pérez-Simón, J.L.Bello, D. Carrera, M.J.
Peñarrubia, E. Abella, A. León, C. Poderós, J.C.
García Ruíz, J. Besalduch, R. Martínez Martínez, I.
Pérez Fernández, P. Ribas, F. Escalante, J. San
Miguel, J. Bladé. Spanish Myeloma Group
(PETHEMA/GEM).
Single vs Tandem Transplant
Randomized Trials
CR
EFS
OS
(%)
(months)
(months)
Attal-2003
34 vs 35
25 vs 30
48 vs 58
(IFM-94)
Cavo-2004
35 vs 48*
+12
44 vs 63**
(Bologna-96)
Sonneveld-2004
13 vs 29
20 vs 22
50 vs 55
(HOVON)
Fermand-2001
39 vs 37*
No benefit
No benefit
(MAG-95)
* CR + nCR
** At 6 years of follow-up
Patients More Likely to Benefit from
Tandem Transplant*
Poor responders to the first high-dose procedure
(failing to achieve at least near-CR)
* Attal et al. NEJM 2003 and Cavo et al. ASH 2004
Aim
To investigate the feasibility and efficacy in
terms of response up-grading and survival
from a second transplant intensification in
patients with chemosensitive disease who
failed to achieve CR or near-CR with a first
transplant in a large multicenter trial.
SPANISH PETHEMA/GEM-2000 TRIAL
VBMCP/VBAD
Bu-MEL or MEL-200 / SCT
1º HDT
CR or nCR
PR or MR
INF/PRED
CVB*/SCT or
2º HDT
"mini-allo**"
*Cyclophosphamide, etoposide, BCNU
INF/PRED
** Fludarabine/Melphalan-140
VBMCP/VBAD
59 refractory patients
HDT-1
493 patients
181 candidates
288 CR post-HDT-1
for HDT-2
24 early deaths
post-HDT-1
· 59 2nd Auto
YES
· 23 Mini-allo
N=82
(45%)
181 candidates for HDT-2
· 28 patient refusal
NO
· 17 insufficient CD34
N=99
· 16 progressive disease
(55%)
· 15 poor PS
· 14 physician decision
· 8 others
Response Status Before Second
Transplant
Overall
TASP
Mini
(n=82)
(n=59)
(n=23)
PR
75 (92%)
54 (92%)
21 (91%)
MR
5 (6%)
3 (5%)
2 (9%)
Progressive
2 (2%)
2 (3%)
-
disease
Response Up-grading with Second HDT
"Auto" vs "Mini"
2nd Auto
Mini
Response
(n=59)
(n=23)
Non-evaluable
1 (1.6%)
-
CR (IF-)
3 (5%)*
6 (26%)*
n-CR (EP-)
1 (1.6%)
-
PR
6 (10%)
1 (4%)
MR
7 (12%)
3 (13%)
No Change
36 (61%)
9 (39%)
Progressive disease
1 (1.6%)
-
Early death (<2m)
3 (5%)**
4 (17%)**
*p=0.01 ** p=0.09
Event free survival from Second HDT Procedure
"Auto" vs "Mini"
1,0
0,9
P=NS
0,8
ingiv 0,7
rvu
S
0,6
tionor
Auto
op 0,5
Pre
tiv 0,4
la
Mini
umu 0,3
C
0,2
0,1
0,0
0
5
10
15
20
25
30
35
40
45
50
55
Months
Overall Survival from Second HDT Procedure
"Auto" vs "Mini"
1,0
0,9
0,8
Auto
0,7
0,6
Mini
aliv
0,5
Surv
0,4
0,3
0,2
0,1
P=NS
0,0
0
5
10
15
20
25
30
35
40
45
50
55
months
Event Free Survival of Patients Candidates to Intensification
Second vs no second HDT
1,0
0,9
0,8
ingiv 0,7
rvu
P=0.006
S
0,6
tionor
op 0,5
Pre
tiv 0,4
laumu 0,3
2 HDT
C
0,2
No 2-HDT
0,1
0,0
01
2
3
45
6
7
Time
Overall Survival of Patients Candidates to Intensification
Second vs no second HDT
1,0
0,9
0,8
2 HDT
ingiv 0,7
rvu
S
0,6
tionor
op 0,5
No 2 HDT
Pre
tiv 0,4
laumu 0,3
C
0,2
0,1
P=0.056
0,0
01
23
45
6
7
years
Patient's Characteristics
Second vs no Second HDT
Yes
No
p
(n=62)
(n=79)
Age (yrs)
55
58
0.001
Hb (g/dL)
10.5
10.8
NS
Creatinine (mg/dl)
1.1
1.6
0.01
Albumin (g/dL)
3.9
4
NS
Calcium (mg/dL)
9.5
9.9
NS
2m (mg/L)
3.5
4.7
0.02
Conclusions
· In more than half of
the patients in whom tandem
transplant was planned the second high-dose procedure
was not performed.
· A dose-reduced intensity allogeneic transplant after an
autologous procedure results in a significantly higher CR
rate than a second autologous intensification.
· With the current follow-up we found no significant
differences in survival between the two modalities of
second transplant
Document Outline