Disclosures for
Heinz Ludwig, MD
In compliance with ACCME policy, the ASH requires the following disclosures to the activity audience:
Research Support/P.I.
Shering Plough, Novartis
Employee
N/A
Louisiana
Orleans,
Consultant
N/A
New
Major Stockholder
N/A
Meeting
Speakers' Bureau
Ortho Biotech, Amgen, Roche
Annual
ASH
Scientific Advisory Board
Ortho Biotech
th 47
N/A = Not Applicable (no conflicts listed)
Presentation includes discussion of the following off-label use of a drug or medical device.
N/A
Thalidomide-Dexamethasone vs. Melphalan-Prednisone
as
First-line Treatment in Elderly Patients with Multiple
Myeloma
Followed by IFN +Thalidomide vs. IFN maintenance
An Interim Analysis
Multicenter, Randomized Study of the Central European Myeloma Study Group
(CEMSG)
H Ludwig, J Drach, E Tóthová, H Gisslinger, W Linkesch, B Jaksic, M Fridrik,
J Thaler, A Lang, R Hajek, N Zojer, R Greil, I Kuhn, B Labar, M Egyed, G Gastl,
R Haidinger, D Lutz, W Lin, R Reisner, M Mistrik, I Spicka, E Gregora, V Scudla, A Hinke
Objectives
Thal-Dex versus MP as first line TX
Primary
Progression free survival
Toxicity/tolerance
Secondary
Response rates
Time to response
Overall survival
Study Design
Newly diagnosed Multiple Myeloma
RANDOMIZATION
Melphalan + Prednisone
Thalidomide + Dexamethasone
Zometa
Zometa
ASSESSMENT
CR, NCR,VGPR, PR, SD
PD
OFF Study
RANDOMIZATION
INF A
Thalidomide + INF A
Zometa
Zometa
Induction Phase
MP
Melphalan 0.25mg/kg days 1-4
+ Prednisone 2mg/kg days 1-4
q 4-6 weeks
Thal-Dex
Thalidomide 200mg/day (escalated to 400mg/day if
feasible)
+ Dexamethasone 40mg days 1-4 (+ days 15-18 on
odd cycles)
q 4 weeks
All Patients: Zometa 4mg, q 4 weeks
Recruitment Overview
Number of Patients
350 Planned
205 Randomized as of December 1, 2005
168 Evaluated for interim analysis
MP - 85, Thal/Dex - 83,
Median Age: 72 years
48% female
Patient Characteristics n=168
Parameter
MP
Thal/Dex
Number of Patients
85
83
Age, Median (range)
72 (55-83)
72 (54-85)
Gender (m/f)
44/41
43/40
Stage
I
4
3
II
26
27
III
55
53
M-Component
IgG
53
51
IgA
20
19
Light Chain
11
11
IgD
1
2
Age Distribution
Median: 72 years
70
60
50
<60
40
60-69
30
70-79
20
>=80
10
0
MP
Thal/Dex
Reasons for Early Withdrawal
Category
Total Number
MP
Thal-Dex
of Patients
Early Death
6
2
4
Serious Adverse Event
6
1
5
Early Withdrawal of
3
2
1
Consent
Second Cancer
1
-
1
Total number*
16
5
11
* p = 0.12, Fisher's exact test
SAE and Deaths on Study
MP
Thal/Dexa
No. of SAE
48
72
No. of Deaths on Study 10
10
Thal/Dex - Number of Cycles Completed
% Patients
51% Patients 5 cycles
100
90
80
70
60
50
40
30
20
10
0
B
C1C2
C3C4C5C6
C7C8
Response Rate
Intent to treat
Parameter
MP n (%)
Thal-Dex n (%)
Number of Pts.
73
73
CR
2 (3%)
6 (8%)
NCR
7(10%)
12(16%)
VgPR
9 (12%)
10 (14%)
PR
18 (25%)
14 (19%)
MR
13 (18%)
11 (15%)
SD
18 (25%)
8 (11%)
PD/Failure
6 (8%)
12 (16%)
Overall CR (CR + NCR)
9 (12%)
18 (25%)
Overall Response (CR to
49 (67%)
53 (73%)
MR) 95% confid. Interval,
55...78%
61...82%
exact, p=0.59, Fisher's T.
Best Response to Treatment
Intent to Treat
Per Protocol ( 2 cycles )
MP
Thal-Dex
MP
Thal-Dex
30
30
25
25
PD/failure
PD/failure
20
SD
20
SD
MR
MR
15
PR
15
PR
VGPR
VGPR
10
10
NCR
NCR
5
CR
5
CR
0
0
CR
12%
25% p=0.087
13%
29% p=0.032
ORR
67%
73% p=0.59
72%
85% p=0.087
Time to Response (Weeks)
Thal-
9
Dex
19
Time to
< 0.008
Response
Time to Best
< 0.0049
Response
18
MP
36
0
1020
3040
Weeks
Progression-free survival
Fig. 4.3
Progression Free Survival-Both Groups Combined
total group
1.0
0.8
Median: 17.6 Months
0.6
te
raS
PF 0.4
0.2
0.0
0
102030
Time [months]
Overall survival
Fig. 4.4 Overall Survival Both Groups Combined
total group
1.0
2 year survival rate: 64%
0.8
te 0.6
raalivrv
Su 0.4
0.2
0.0
0
102030
Time [months]
Thalidomide Dose at Baseline and during further TX
% Patients
100
92%
90
80
70
60
50
40
38%
37%
36%
35%
32%
30
20
10
0 50 200
50
400 50
400 50
400 50
400 50
400
Baseline
C2
C3
C4
C5
C6
Fig. 4.5Time to
Time to thromboem
Thromboembolic
bol
Event ic- ev
T ent
hal-Dex Patients
1.0
Thal/Dex group
n = 75,
11 events
0.8
te 0.6
era
idenc
Inc 0.4
0.2
0.0
010
20
30
40
Time [months]
Toxicity Grade III-IV (NCCN Toxicity Scale)
Assessed in 168 Patients
Parameter
MP
Thalidomide- Significance*
Dex
p=
Leukopenia
12 (14%) 2 (2.5%)
0.0097
Thrombocytopenia 5 (6%)
2 (2.5%)
0.44
Neuropathy
5 (6%)
16 (19%)
0.01
Psychologic
5 (6%)
12 (14%)
0.077
Skin
3 (4%)
10 (12%)
0.046
Thrombembolic
6 (8%)
17(20%)
0.051
*Fisher's exact test, two sided
Summary
Similar ORR (67% vs. 73%)
Tendency for higher CR+NCR in Thal-Dex group (12% vs 25%,
p=0.087); (13% vs. 29%, p < 0.032); analysis per protocol.
Time to response shorter in patients on Thal-Dex (9 vs. 18
weeks, p=0.008)
G 3&4 Neuropathy, Thromboembolic Events, and Rash more
frequent in patients on Thal-Dex
G 3&4 Leukopenia significantly increased in patients on MP
Thal-Dex is at least as effective as MP, relatively well tolerated
and induces remissions much faster than MP in elderly
patients with MM
We thank the patients for participating in the study
... the other contributors from 30 centers in Austria
Czech Republic, Hungary, Slovakia and Croatia
...and you for your attention
Progression-free survival
Progression Free Survival Both Groups Combined
by treatment arm
1.0
0.8
0.6
te
Thal/Dex
Thal-Dex
raS
PF 0.4
MP
MP
0.2
0.0
010
20
30
Time [months]
Fig. 3.1
Extent of treatment form documentation
40
35
30
25
n = 112
n 20
15
10
5
0
C2
C3
C4
C5
C6
C7
C8
C9
A E03r
30.03.05