Tandem Autologous Transplant versus Reduced
Intensity Conditioned Allogeneic Transplant (Allo-RIC)
in Chemosensitive Patients with Multiple Myeloma
(MM) not Achieving Complete Remission (CR) or Near-
CR with a First Autologous Transplant. Results from a
Spanish PETHEMA/GEM Study
J. Bladé, 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, J. San Miguel. Spanish
Myeloma Group (PETHEMA/GEM).
Disclosures for All Authors
Research Support
Not applicable
Employee
Not applicable
Consultant
Not applicable
Major Stockholder
Not applicable
Speakers Bureau
Not applicable
Honoraria
Not applicable
Scientific Advisory Board
None
Rationale
In
two
prospective
randomized
trials,
double
autologous transplant was superior to a single
transplant, particularly in patients failing to achieve at
least VGPR. However, there was no survival plateau
with the tandem autologous approach.
Promising results have been reported with allogeneic
transplantation
using
dose-reduced
intensity
conditioning ("Allo-RIC"), especially after debulky with
an autologous transplant.
Aim
To investigate the efficacy in terms of
response improvement and survival from a
second transplant intensification (2nd "auto"
vs. "Allo-RIC") in patients with chemosensitive
disease who failed to achieve CR or near-CR
with a first transplant.
Spanish PETHEMA/GEM-2000 Trial
VBMCP/VBAD
Bu-MEL or MEL-200 / SCT
CR or nCR
PR or MR
IFN/PRED
CVB* or MEL-200 /SCT
or "allo-RIC**"
*Cyclophosphamide, Etoposide, BCNU
IFN/PRED
** Fludarabine/Melphalan-140
Spanish PETHEMA/GEM-2000 Trial
215 candidates for HDT-2
YES
NO
N=111 (55%)
N=103 (45%)
· 28 patient refusal
· 17 insufficient CD34
· 16 progressive disease
· 85 2nd Auto
· 15 poor PS
· 26 Allo-RIC
· 14 physician decision
· 11 others
· 3 deaths
Response Status at the Time of Second
Transplant
Overall
2nd Auto
Allo-RIC
Response
(n=111)
(n=85)
(n=26)
PR
103 (93%)
79 (93%)
24 (93%)
MR
5 (4%)
3 (3.5%)
2 (7%)
Progressive
3 (3%)
3 (3.5%)
-
disease
Response Up-grading with Second HDT
"Auto" vs."Allo-RIC"
2nd Auto
Allo-RIC
Response
(n=85)
(n=26)
Non-evaluable
1 (1%)
-
CR (IF-)#
9 (10%)*
9 (35%)*
n-CR (EP-)
7 (8%)
-
PR
8 (9%)
2 (8%)
MR
9 (10%)
2 (8%)
No change
45 (53%)
9 (35%)
Progressive disease
2 (2%)
-
TRM
4 (5%)**
4 (15%)**
*p=0.01 ** p=0.08
#IF: immunofixation : electrophoresis
EFS
2nd Auto vs. Allo-RIC
1.0
0.9
0.8
0.7
Allo-RIC
0.6
rvival 0.5
Su
2nd Auto
0.4
0.3
0.2
0.1
p=NS
0
0
102030
405060708090
100
Months
Survival
Auto vs. Allo-RIC
1.0
0.9
0.8
Allo-RIC
0.7
0.6
2nd Auto
rvival 0.5
Su
0.4
0.3
0.2
0.1
p=NS
0
0
1020
30
4050
6070
80
90
100
110
Months
Double Autologous Transplant vs.
Auto/Allo-RIC
CR rate
EFS
OS
Author
No. Pts
(%)
mos.
mos.
Garban et al.
32.5 vs. 32.6 31.7 vs. 35
42.7 vs. 35
166 vs. 51
Blood 2006
(p=NS)
(p=NS)
(p=0.07)
Bruno et al.
26 vs. 55
29 vs. 35
54 vs. 80
82 vs. 80
NEJM 2007
(p=0.004)
(p=0.02)
(p=0.01)
Present
10 vs. 35%* 48 vs. NR** 80 vs. NR**
85 vs. 26
series
(p=0.01)
(p=NS)
(p=NS)
*Response improvement with second transplant
** Not reached
Double Autologous Transplant vs. Auto/Allo-RIC
Study Design
Author
Inclusion Criteria
Conditioning
Garban et al.
High-risk
Fludarabine/
Blood 2006
(high 2M, 13q-)
Busulfan/ ATG
Bruno et al.
All patients
TBI (2 Gy)
NEJM 2007
No CR/nCR with
Fludarabine/
Present series
1st transplant
MEL-140
Conclusions
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 no significant differences in
survival were observed between the two modalities of
second transplant. However, there is an EFS and OS
plateau with the "Allo-RIC" procedure.