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Jointly sponsored by Postgraduate Institute for Medicine, the
International Myeloma Foundation, and Clinical Care Options, LLC
Multiple Myeloma:
Finding Your Way
gy Through the Treatment Maze--Selecting
the Best Treatment in the Era of Novel Agents
Friday, December 5, 2008
6:30 PM - 9:00 PM
Moscone Center
San Francisco, California
Supported by educational grants from Celgene, Genzyme Transplant, Lilly,
Millennium Pharmaceuticals, Inc., and Ortho Biotech.

Role of Transplantation and
and
Maintenance Therapy
Philippe Moreau, MD
University Hospital
yp
Hôtel-Dieu
Nantes, France

Survival Improvement in the '90s in Young Patients: ASCT
Brenner H, et al. Blood. 2008;111:2521-2526.

IFM90 Trial: ASCT vs Conventional Dose: Overall Survival
Attal M, et al. N Engl J Med. 1996;335:91-97.

MRC VII Trial: Intensive Therapy vs Standard Therapy: PFS
Child JA, et al. N Engl J Med. 2003;348:1875-1883.

ASCT vs Conventional CT
Results of
of Randomized
Randomized Studies
Author
N of Pts
Age
CR/VGPR Rate
EFS
OS
Attal 1996
200
65
YES
YES
YES
Fermand 1998
185
< 55
YES
YES
NO
Child 2003
401
65
YES
YES
YES
Palumbo 2004
195
< 70
YES
YES
YES
Fermand 2005
190
55-65
YES
YES
NO
Blade 2005
164
< 65
YES
YES
NO
Barlogie 2006
516
70
NO
NO
NO

Results Achieved
Achieved With
With Single
Single ASCT
ASCT
ASCT
CC
CR
15-25%
< 10%
VGPR
40-50%
< 20%
Median PFS
25-35 mos
15-20 mos
Median OS
55-60 mos
42-60 mos

ASCT vs CC
·
ASCT is superior to CC in terms of
- CR/VGPR
6/7 studies
- EFS/PFS
5/7
-OS
3/7
·
The benefit from ASCT is related to a better quality of response
New definition of response criteria (EBMT/IMWG, Bladé J, et al. Br J
Haematol; Durie BG, et al. Leukemia)
·
ASCT can also be offered as a salvage treatment at relapse (mostly in
younger patients)

IFM 9502 Trial: Melphalan vs Melphalan + TBI: Overall Survival
Moreau P, et al. Blood. 2002;99:731-735.

IFM 94: OS if Response to 1st Graft < 90%
P < .001
Double-transplant group (n
= 128)
Single-transplant group (n = 84)

IFM 94: OS if Response to 1st Graft > 90%
P = .7
Double-transplant group (n
= 46)
Single-transplant g
pgroup (n = 81)

IFM 94: Conclusions
Double transplantation should be recommended for
patients failing to achieve VGPR or CR after the 1st
tl
transpl t
an .
Attal M, et al. N Engl J Med. 2003 349
;
2495
:
2502
-
.

Cytogenetic + 2M Model
OS
No t(4;14), no del(17p), ß2M < 4, no del(13)
155 pts
No t(4;14), no del(17p), ß2M <4
< 4, del(13)+
110 pts
No t(4;14), no del(17p), ß2M > 4, no del(13)
74 pts
No t(4;14), no del(17p), ß2M > 4, del(13)+
69 pts
t(4;14) or del(17p)>60%, ß2M < 4
63 pts
t(4;14) or del(17p)>60%, ß2M > 4
42 pts
Avet-Loiseau H, et al. Blood. 2007;109:3489-3495.

Attal M, et al. N Engl J Med. 1996;335:91-97.

IFM 99: Impact of Overall Response on EFS and
OS
P = 8.10 -6
< PR
Median 24 mos
PR
Median 32 mos
VGPR
Median 36 mos
CR
Median 42 mos
EFS
4-Year OS
< PR
65%
PR
67%
VGPR
76%
CR
80%
OS
P = .0003
Harousseau J-L, et al. ASH 2006.
Abstract 3077.

Prognostic Impact of CR Obtained Before and After ASCT:
GEM2000 Clinical Study: Single ASCT
EFS
OS
1,0
1,0
CR vs nCR or PR,
CR, n = 278
P < 10-5
0,9
0,9
nCR, n = 124
CR vs PR, P = .07
PR, n = 280
0,8
0,8
PD, n = 25
0,7
0,7
Surviving 0,6
ree
urviving 0,6
F
S
0,5
0,5
Event 0,4
0,4
Proportion
CR vs. nCR, P = .01
0,3
-5
oportion
tive
CR vs PR, P <10-5
at
CR vs PR, P < 10
Pr
0,3
nCR vs PR, P = .04
0,2
Cumul
0,1
0,2
Cumulative 000,0
0,1
0
12
24
3648
607284
96
0
1224
36
4860
72
84
96
Lahuerta JJ, et al. J Clin Oncol. 2008 Nov 10. [Epub ahead of print].

IFM 99-02
-Patients 65 years, de novo
- 0 or 1 adverse prog
pgnostic factors (chr 13, ß2M)
VAD
VAD
VAD
HDM 140 + ASCT
HDM 200 + ASCT
Contro
Contr l
Pamidronate
Pamidr
= Arm A
Pamidronate
+ Thalidomide
= Arm B
= Arm C

Overall Survival According to Treatment Arm
With thalidomide
Without
W
thalidomide
4-year OS
With thalidomide maintenance: 87%
ii
Without thalidomide
i
ma ntenance: 75%
Attal M, et al. Blood. 2006;108:3289-3294.

Maintenance TT With Thalidomide
Post ASCT
PFS
N
Initial
CR Rate
OS
Dose
Barlogie B, et al. N Engl
Engl J
668
400
62% vs 43%
5-yr PFS
NS
43%
Med. 2006;354:1021-1030.
56% vs 44%
Attal M, et al. Blood.
597
200
68% vs 56%
3-yr EFS
4-yr OS
56%
2006;108:3289-3294.
52% vs 36%
87% vs 75%
Abdelkefi A, et al. Blood.
140
100
67% vs 51%
2-yr PFS
3-yr OS
2008;111
111:1805-1810
84% vs 70%
1810.
85% vs 65%
Spencer A, et al. ASH 2006.
243
200
24% vs 15%
2-yr PFS
2-yr OS
Abstract 58.
66% vs 40%
58.
91% vs 80%

IFM 2005-02: Lenalidomide as Maintenance Therapy After
ASCT for MM
MM, 662 Patients, Completed 08/2008
Phase III randomized, placebo-controlled trial
Patients < 65 years, with non-progressive disease, 6 months after ASCT
in first line
Randomize
Consolidation
Lenalidomide
Lenalidomide 25
25 mg/day
mg/day PO
PO, Days
Days 1-21 of
every 28 days for 2 months
Lenalidomide
10 15
-
mg/day PO
Placebo until relapse
PO,
continuous dosing until
relapse
Primary endpoint:
endpoint: time to relapse.
Secondary endpoints: CR rate, PFS, OS, feasibility of long-term lenalidomide

Ongoing PETHEMA/GEM 2005 TRIAL
Symptomatic MM Patients < 65 Years
1st Randomization
VBMCP/VBAD
THALIDOMIDE/
THALIDOMIDE/
X 4
DEX
DEX/
BORTEZOMIB
X 6
BORTEZOMIB
X2
X 2
X6
X 6
ASCT (Melp
(phalan 200)
2nd Randomization
INTERFERON--2b
THALIDOMIDE
THALIDOMIDE/
X 3 yrs
X 3 yrs
BORTEZOMIB X 3 yrs

Ongoing HOVON 65 MM/GMMG-HD4
Accrual goal: 800 patients
MM Stage II or III, Age 18-65
Randomization
3x
3 x VAD
VA
3xP
3 x AD
PA
CAD + GCSF
CAD + GCSF
MEL 200 + PBSCT
MEL 200 + PBSCT
Depending on local
Depending on local policy for
policy for patients PR MEL
patients PR MEL 200 +
Allogeneic Tx
200 + PBSCT
PBSCT
Thalidomide
Bortezomib
50 mg/day for
1.3 mg/m2/2 weeks for
2 years maintenance
2 years maintenance

CONCLUSION
Currently, for younger patients out of a clinical trial
Induction (with a VEL/DEX-based regimen?)
ASCT prepared by mel200
Post-ASCT maintenance with thalidomide (lenalidomide?)
() 1 year

Role of Transplantation and
and
Maintenance Therapy
Philippe Moreau, MD
University Hospital
yp
Hôtel-Dieu
Nantes, France