HOVON 50/GMMG-HD3 study
A randomized phase III study on the effect of
Thalidomide combined with High Dose Melphalan in
myeloma patients under 66 years
Interim analysis: Sydney, april 2005
Henk Lokhorst
Hovon: H. Lokhorst, P. Sonneveld. B. vd Holt
GMMG: H. Goldschmidt, F. Cremer. A. Glasmacher, I. Breitkreuz
HOVON 50/GMMG-HD3
· November 2001- april 2005
· Inclusion 1050 patients
· Phase III in patients 65 years
MM stage 2/3; WHO performance 0-3
· Interim analysis march 2005 on 414 patients
registered before april 2004
HOVON 50/GMMG-HD3 study
VAD (3x)
TAD (3x)
vs
Iv push
Thal 200-400mg/daily
Randomization
CAD + G-CSF
Stem cell collection
Cyclo/adria/dex
HDM 1-2x
Auto PBSCT
200mg/m2
HLA-id Sib
NonmyeloST
-IFN
Thalidomide
Maintenance/
vs
200cGy
Thrice/weekly
vs
50 mg/daily
Consolidation
Objectives of interim analysis
· Efficacy of DVT prophylaxis with low dose LMWH
during induction with TAD (earlier analysis)
· Impact of thalidomide on stem cell collection
· Impact of thalidomide on response
- after induction (VAD versus TAD)
- after intensification (1st HDM)
· (Progression free and overall survival)
· (Feasibility of "Upfront" Nonmyeloablative Allo-SCT)
Patient characteristics
VAD
TAD
Male/Female
119/84
135/68
Total
203
203
Stage 2 A/B
46/0
38/3
,, 3 A/B
128/29 (78%)
139/23 (80%)
Age median
55.7 years
55.7 years
range
32-65
34-65
Prognostic factors
to be deter
mined
DVT prophylaxis during TAD
· Low dose low molecular weight heparin
(nadroparine 2850 i.e.) is prescribed during
induction with TAD from day 0 untill 5-6 weeks
after the 3rd TAD (stop 10 days before CAD)
· Analysis performed earlier on 212 patients
DVT incidence during induction
25
N
O
VAD
201
11
AD+thal
211
19
ArmA: DVT
8 (4%)
Logrank P=.15
20
Arm B: DVT
16 (8%)
During prophylaxis: 12 (6%)
15
percentage
P=0.15
10
AD+thal
Cumulative
5
VAD
0
0
2
4
months 6
At risk:
VAD 201
194
191
187
AD+thal 211
197
187
185
Stem cell collection after CAD
·
Cyclophosphamide 1000 mg/m2
day 1
Adriamycin
15 mg/m2
day 1-4
Dexamethasone
40 mg
day 1-4
G-CSF
10 µg
day 5-12
Arm A
Arm B
P-value
Days from
11 (9-17)
11 (7-19)
N.S
CAD to leuc
No of leuca-
1 (1-7)
1 (1-7)
N.S
pheresis
CD 34+
9.9 (9-43)
7.9 (2-33)
0.007
collected
Failure to
2
2
N.S.
collect
Feasibility
Arm A
Arm B
P-value
(n=203)
(n=203)
CAD not eligible
3
3
ns
HDM not eligible
4
4
ns
Drop out due to
17 (8%)
30 (15%)
P = 0.1(act)
excessive toxicity
Thalidomide stop
9 (4%)
during TAD
DVT incidence
4%
8%
P =0.15
% of patients
85%
81%
ns
treated with HDM
Response after induction
VAD
TAD
P-value
%
%
Chi2
PR
60
73
<0.001
CR
3
7
0.11
Total
63
80
0.001
Response after HDM 200 (first)
Arm A
Arm B P-value
%
%
Chi2
PR HDM
75
82
0.8
Intention
64
59
to treat
CR HDM
13
19
0.3
Intention
11
15
to treat
Total
88
91
0.4
Intention
75
74
to treat
Overall survival HOVON 50/GMMG-HD3
Overall survival (extended)
Treatment arm
100
.
75
percentage
50
N=406
Cumulative
25
N
d
??
203
35
??
203
34
0
0
6
12
18
months 24
At risk:
?? 203
189
166
121
77
?? 203
188
166
124
83
HOVON 54 (Auto/Allo)
VAD (3x)
TAD (3x)
vs
Iv push
Thal 200-400mg/daily
Randomization
CAD + G-CSF
Stem cell collection
Cyclo/adria/dex
HDM 1x
Auto PBSCT
200mg/m2
Hovon 54
HLA-id Sib
NonmyeloST
-IFN
Thalidomide
Maintenance/
vs
200cGy
Thrice/weekly
vs
50 mg/daily
Consolidation
HOVON 54
· Inclusion:
- 64 patients (expected 90 by end of 2005)
· TRM:
- 3 patients (5%) from GvHD
- No efficacy analysis yet
Conclusions
· LMWH effectively prevents DVT during thal+AD
· Thalidomide does not hamper stem cell collection
· Upfront auto/allo seems feasible with low TRM, however the
efficacy and long term toxicity/TRM as compared to Auto-PBSCT
has to be determined
· Thal + AD induces a significant higher response but this
effect is completely compensated by HDM
It is questionable if TAD (alone) should be
recommended as induction therapy for intensive
treatment
Document Outline