Phase III Studies That have
have been
Completed, Ongoing and Planned by
Various Northern European Groups in
Multiple Myeloma
XIIth IMWS
Pieter Sonneveld
The Netherlands
Trials with conventional agents in
t
pa i
tients l
e ii
lig bl
ible for hih
high dt
-dose h
therapy
UK myeloma VII : the importance of CR after
ASCT
Child et al. NEJM 2003;348:1875-83
DSMM V:Newly diagnosed MM 60 yrs (n = 798)
Id /D
a ex
Ida/Dex
Ida/Dex
Ida/D
da/ ex
e
IEV
1H
1. D
HD-Ml
Mel
200 mg/m²
Standard
High risk
risk
HLA identical sibling/MUD
2. HD-Mel
yes
no
200 mg/m²
Allo-SCT
2. HD-Mel 200 mg/m²
R
Dex + IFN
Peg-IFN
IFN@
Risik-Stratifikation DSMM V Trial
Patients im Tandem-Auto/AutoAllo-Protokoll 2/02 3/07: n = 187
Median Age, y (Range)
53 (30 60)
Ml
Male (%)
(%)
56
Durie-and-Salmon stage III (%)
76
Tandem
T
HD
HD--Mel
Mel
Auto/Allo
n, (%)
%
69 (36)
11
119 (64)
Allo-SZT vom VUD
n.a.
70 (59)
CR
25 %
49 %
ORR
72 %
67%
Overall survival @ 3 Jahre
75 %
63 %
GMMG-HD2 trial High-dose therapy
1999-2002
Randomisation I: VID vs. VAD
until CR or plateau, max. 6 cycles
>/= SD VAD/VID
Randomisation II
HD-cyclophosphamide
(ifosfamide) + G-CSF
Leukapheresis
CD34+-selection optional
Melphalan
2 Cycles
Cycles
1 cycle
Melphalan
200 mg/m²
+ PBSCT
Interferon-
Interferon-
GMMG-HD2 Single vs. Double HDT:
EFS & OS
double
single
HOVON 24 single vs double intensive
3-4 VAD push
Allo-SCT if HLA-id
sibling
R
Cl
Cyclophosph
i
am d
ide
Cl
Cyclophosph
i
am d
ide
4g/m2 + G-CSF
4g/ m2 + G-CSF
Mlhl
Melphalan
Mlhl
Melphalan
140mg/m2 (2 x 70)
140mg/m2 (2 x 70)
6
Cy/TBI + ASCT
Interferon 3*106 IU
s.c 3x/week
Interferon 3* 106 IU
s.c. 3/
3x/week
PFS, TTP, OS by cytogenetic
del13/13q-
Overall survival
Event free survival
Chromosome 13 abnormality (13q or -13)
Chromosome 13 abnormality (13q or -13)
100
100
no
75
75
yes
percentage
50
percentage
50
ive
ive
no
25
25
Cumulat
N
F
Cumulat
N
F
yes
no
125
62
no
125
101
yes
25
20
yes
25
25
Logrank P<.001
Logrank P=.006
0
0
0
24
48
72
months 96
0
24
48
72
months 96
At risk:
At risk:
no 125
99
76
19
3
no 125
65
29
5
0
yes 25
13
9
1
0
yes 25
9
1
0
0
Progression free survival
TTP from start VAD, [mo] - 1
Chromosome 13 abnormality (13q or -13)
Chromosome 13 abnormality (13q or -13)
100
100
yes
N
F
no
125
77
yes
25
23
Logrank P<.001
75
75
no
ercentage
ercentage
p
50
p
50
no
25
yes
25
Cumulative
N
F
Cumulative
no
101
77
yes
20
20
Logrank P<.001
0
0
0
24
48
72
months 96
0
24
48
72
months 96
At risk:
At risk:
no 101
56
26
2
0
no 125
80
37
7
0
yes 20
6
1
0
0
yes 25
9
1
0
0
Segeren,Blood, 101:2144-51, 2003
Thalidomide trials in patients eligible
fh
for i
high dt
-dose h
therapy
Myeloma IX Intensive pathway
Randomise
Bi
h
sp
h
osp onat
Clodronate
Zoledronate
te:
Clodronate
VS
Zoledr
VS
C-VAD
C-TD
VS
4-6 courses
4-6 courses
HDM200
Chemotherapy:
+
PBSCT (autograft)
Patients with potential sibling donors will also be offered an
LIC allogenei
e c Procedur
ocedu e (mini
(
all
a ogr
og af
a t)
t)
Randomise
Thalidomide
No Thalidomide
Maintenance:
VS
Phase 3: TAD vs VAD (HOVON-50)
Final Analysis
Analysis
VAD (3x)
TAD (3x)
vs
Iv push
Thal 200 mg/daily
556 patients
Iv push
Thal 200 mg/daily
p
CAD +G
+ G-CSF
87%
Cyclo/adria/dex
HLA-id
RIC
Sib
HDM 1-2x
82%
N=109
200mg/m2
20%
-IFN
Thalid
id
om e
34%
46%
Thrice/weekly
50 mg/daily
Lokhorst et al. ASH 2008 (abstract 157)
Phase 3: TAD vs VAD (HOVON-50)
Fi
l
na A
l
na
i
ys s
TAD
VAD
P
CR
30%
21%
0.03
VGPR
65%
54%
<0 01
.
PR
87%
79%
<0.01
EFS
33 months
22 months
<0 001
.
PFS
33 months
25 months
<0.001
OS
59 months
62 months
09
0. 6
96
n=109 received a non-myeloablative allogeneic transplant after HDM 1 and were
entered onto another trial
Thalidomide resulted
resulted in significantly higher
higher response
response rates
rates, improved EFS
and PFS, however, this did not translate into better overall survival
Lokhorst et al. ASH 2008 (abstract 157)
Landmark analysis
best response achieved within 12 months
HOVON 50 MM: survival from 12 months after randomisation
EFSC: EFS, [mo] (censored at alloSCT) [start = 12 mo]
PFS: Progression free survival [m] [start = 12 mo]
Best response within 12 months
Best response within 12 months
100
100
75
75
age
age
percent
50
percent
50
CR
CR
ulative
VGPR
ulative
VGPR
Cum
25
Cum
25
N
F
PR
N
F
PR
CR
43
20
CR
43
20
VGPR
139
84
VGPR
139
87
PR
102
67
PR
102
71
EFS
0
0
EFS
PFS
0
12
24
36
48
months 60
0
12
24
36
48
months 60
At risk:
At risk:
PFS
CR 43
38
25
14
6
0
CR 43
38
25
14
6
0
VGPR 139
102
67
30
9
2
VGPR 139
104
69
31
9
2
PR 102
61
37
21
6
1
PR 102
64
38
21
6
1
25 Nov 2008 - 11:05:42
25 Nov 2008 - 11:05:43
OS: Overall survival [m] [start = 12 mo]
Best response within 12 months
100
CR
75
age
VGPR
percent
50
PR
ulative
Cum
25
N
F
CR
43
6
VGPR
139
42
PR
102
38
0
0
12
24
36
48
months 60
At risk:
CR 43
42
37
26
10
0
VGPR 139
129
108
64
22
5
PR 102
90
76
47
15
3
25 Nov 2008 - 11:05:43
OS
Lokhorst et al. ASH 2008 (abstract 157)
Reduced OS from relapse after Thal exposure
Ol
Overa lll
i
surv
l
va from progressi /
on
l
re apse
Treatment arm
100
P=0 0
. 1
01
75
rcentage
A:noThal
pe
50
B:+Thal
mulativeuC 25
N
D
A:noThal
179
81
B:+Thal
133
79
Logrank P=.01
0
0
12
24
36
months 48
At risk:
A:noThal 179
108
57
25
3
B:+Thal 133
72
34
13
5
1 Dec 2008 - 09:26:52
Lokhorst et al. ASH 2008 (abstract 157)
GMMG-HD3: TAD vs VAD
MM Stage II or III, Age 18-65
Rd
Randomi t
sa ition
Thalidomide
3 x VAD
3 x TAD
400 mg
Mobilisation &
CAD
Leukapheresis
CAD
MEL 200 + PBSCT
MEL 200 + PBSCT
All
i
ogene c T
MEL 200 + PBSCT
x
PBSCT
MEL 200 + PBSCT
2Gy + Fludara
HOVON 54
EBMT NMAM2000
-Interferon
Thalidomide
9 Mio. U/Week
50 mg
GMMG-HD3: No difference PFS or OS
Better TtE , itt
p=0.0116
Bortezomib trials in patients eligible
fh
for i
high dt
-dose h
therapy
HOVON 65 MM / GMMG-HD4 Phase 3 study:
PAD vs VAD
VAD as i d
n
ti
uc on t
t
rea ment
MM Stage II or III, Age 1865
Randomization
3xV
3 x AD
VA
3xP
3 x AD
PA
CAD + GCSF
CAD + GCSF
MEL 200 + PBSCT
MEL 200 + PBSCT
Depending on local
Depending on local
Allogeneic
li
po cy for pati
tients PR
li
po cy for pati
tients PR
MEL 200 + PBSCT
Tx
MEL 200 + PBSCT
Thalidomide
Bortezomib
50 mg/day for
13m
1.3
g/m2
mg/m / 2 weeks
2 years
for 2 years
maintenance
maintenance
Sonneveld et al. ASH 2008 (abstract 653)
PAD vs VAD Response rates
PAD
VAD
P
(n=150)
(n=150)
Response after induction
CR/nCR
5%
1%
-
VGPR
42%
15%
<0.000001
PR
83%
59%
0.000014
Responses after first ASCT
CR/nCR
23%
9%
0.0015
VGPR
80%
50%
0 0019
.
PR
93%
80%
0.0021
PA
PAD significantly
significantly increased
increased the rate
rate of
of CR+nCR and
and VGPR
pre- and post-transplant compared with VAD
No impact of t(4;14) or 13q-
Sonneveld et al. ASH 2008 (abstract 653)
Protocol for newly diagnosed MM < 60 yrs.
DSMM XI
optional Dex
Dex
VelCyDex
VelCyDex
VelCyDex
y
IEV
1H
1. D
HD-Ml
Mel
200 mg/m²
Standard
High risk
risk
HLA identical sibling/MUD
2. HD-Mel
yes
no
200 mg/m²
Allo-SCT
2. HD-Mel 200 mg/m²
R
R
R
Nil
Vel weekly
Nil
Vel weekly
Nil
Vel weekly
DSMM XI Tr
T ial:
r
VCD as an induction regimen
Response to treatment at day 63
Würzburg
n
Response to VCD
n (%)
center,
center n=31
16
14
12
ORR
168 (84.0)
()
10
8
6
4
n
n
n
n
CR
25 (12.5)
2
0
=
=
=
=
CR
VGPR
PR
SD
4
1
6
6
5
PR
143 (71.5)
CR+VGPR = 61 %
5)
MR
11 (5.5)
SD
17 (8.5)
PD
4 (2.0)
Knop et al. ASH 2008
Response to
to VCD
VCD treatment with respect to
cytogenetic aberrations (n=160)
%
100
PR)
90
(>
80
ent
70
60
treatm
50
VCD
40
ot
30
20
10
tresponse
0
Bes
no
13q-
t(4;14)
17p-
FISH analysis available
n (%)
Overall
160 (80)
dl
de (13
l(13 )
q
56 (28)
t(4;14)
16 (8)
Knop et al. ASH 2008
del(17p)
20 (10
NMSG 15/05 BORTEZOMIB CONSOLIDATION
STUDY
·
Patients randomized 3 months
months post ASCT
ASCT to
to control
control or
or
consolidation with bortezomib, 20 doses during 21 weeks
·
1.3 mg/sqm twice weekly for 2 weeks followed by one week's
rest for a total of two cycles followed by weekly injections for
3 weeks followed by 1-week rest, repeated
,p
4 times
·
Primary end point EFS
·
378 out of 400 patients included so far, study will be closed in
April
·
Response, toxicity and feasibility data will be presented at the
end of this year and survival data 2010
Conclusions
· Combination regimens including at least one novel agent,
appear to be superior to standard conventional chemotherapy
like VAD
· No effect of 2nd HDM in German trial
· Thalidomide prolongs EFS but not OS
· Post-induction response rates are further increased by novel
t
agen + HDT/ASC
A
T, achi
hieving CR/nCR rates of >50%
· Promising CR/nCR/VGPR rates with Bortezomib
· Impact on overall survival with the novel induction regimens
remains to be determined
New trials in patients eligible for hig
ggh-
dose therapy
DSMM XII Trial: RAD as an Induction
Treatment
T
in Newly Diagnosed
Diagnosed MM
Allo-SCT
Treo/Flu
R-Maint.
Mel 200
* if patient`s choice and if HLA-
RAD RAD RAD RAD
Re-
matched donor available
staging
CE
mg/m²
Mel 200
R-Maint.
mg/m²
PBSCT
d 29
d 85
d 135
d 1
d 57
d 120
28 56 days
56 84 days
56 112 days
12 months
Screening
GMMG-HD5
Inclusion
Randomization9)
Induction 1)
3 x PAd2)
A1 + B1
3 x VCD3)
A2 + B2
Mobilization
CAD4)
C
+ leuk
eu aph
ap eres
e i
s s
PBSCT
HDM + TPL5)
2. PBSCT
(if no CR)
HDM + TPL5)
Consolidation
Consolidatio
3xR
3 x d6)
Rd
A1
B1
A2
B2
Lenalidomide7)
Maintenance
Lenalidomide7)
Lenalidomide7)
Lenalidomide7)
if no CR
if no CR
Free light chain (C
(FL )
C)
+ MRD8) diagn. every
for 2 years
for 2 years
3 months
1) Risk assessm. within first 4 weeks; high risk patients proposed to go off protocol and in an experimental phase II trial (allogeneic transplantation)
2) PAd = Bortezomib (PS-341, Velcade) 1,3mg/m² d1,4,8,11; Adriamycin 9mg/m², d1-4; Dexamethasone 20mg, d1-4, d9-12, d17-20
3) VCD = Bortezomib (PS-341, Velcade)
V
1,3mg/m²
3mg/m² d1
d1,4,8,11; Cyclophosph
Cy
amid 900mg/m², d1, Dexamethasone 40mg, d1
d1-2d
2, 4
d4-5d
5, 8
d8-9, d11-12
4) CAD = Cyclophosphamide 1g/m² d1; Adriamycin 15mg/m², d1-4; Dexamethasone 40mg, d1-4;
5) HDM + TPL = High Dose Melphalan 200mg/m² and autologous stem cell transplantation
6) Rd = Lenalidomide (Revlimid) 15mg/d, d1-21; Dexamethasone 20 mg/die d1-4, 8, 15, 22;
7) Lenalidomide 10mg/d
8) MRD = minimal residual disease
9) randomization to one of four treatment strategies A1, B1, A2, B2: A1= PAd induction, lenalidomide maintenance for 2 years; B1= PAd induction, lenalidomide maintenance if
no CR; A2= VCD induction, lenalidomide maintenance for 2 years; B2 = VCD induction, lenalidomide maintenance if no CR
Flowsheet 18.02.09
European Intergroup study in transplant-
eligible p
gpatients challenging transplant:
p
study
VCD (3 cycles)
design
Bortezomib: 1.3 mg/m2, d 1, 4, 8, 11
Cyclophosphamide: 750 mg/m2, d 1
Dexamethasone:
Dexamethasone: 20
20 mg
mg, d 1245891
1, 2, 4, 5, 8, 9, 1
11, 12
12
CTX : 24 g
PBSC HARVEST
Mi i
n mum: 41
4 x 06
10 CD34+/kg
1st Rand
VMP (4 cycles)
Bortezomib: 1.3 mg/m2,
MEL 200
2 x MEL 200
d 1, 4, 8, 11
11, 22, 25, 29, 32
Melphalan: 9 gm/m2, d 14
Prednisone: 60 mg/m2, d 14
2nd Rand
Revlimid
Revlimid/Dex
Until relapse
Until Relapse
Trials in patients not eligible for
tl
transplant i
l
nc udi
ding novel agents
Melphalan-Prednisone-Thalidomide to
Newly Di
d
agnose P ti
a ents with
ith
Multiple Myeloma
A Placebo
Placebo Controlled
Controlled Randomised
Randomised
Phase 3 Trial from the Nordic
Myeloma Study
yy Group
NMSG #12
Waage et al. ASH 2007 (abstract )
NMSG #12: Response itt
35
30
25
20
placebo
15
thal
centage
a
c
10
per
5
0
nCR/CR
VGPR
PR
MR
NR
Thal
responses>PR: 57 %
Placebo responses >PR: 40%
NMSG #12: TTP, PFS and OS
Time to progression
Pi
Progression-free survival
1.0
1.0
P<0,03
0.8
0.8
Thal
0.6 thal
0.6
0.4
.40
0.2
placebo
0.2
0.0
0.0
10
20
30
40
50
months
10
20
30
40
50
months
Number at risk
Number at risk
trt = A
105
48
15
8
3
trt = B
106
51
27
11
6
trt = A
105
48
15
8
3
tt
trt = B
106
51
27
11
6
trt = A
trt = B
trt = A
trt = B
Overall survival, by treatment
1.0
80.
0.6
0.4
0.2
00.
10
20
30
40
50
months
Number at risk
trt = A
136
90
50
31
17
trt = B
130
92
53
24
14
Waage et al. ASH 2007 (abstract )
trt = A
trt = B
Melphalan + Prednison versus
Melphalan
p
+ Prednison + Thalidomide in
induction therapy for multiple myeloma in
elderly patients: final analysis.
The HOVON 49 study
Weijermans et al. ASH 2008 (abstract )
HOVON 49 : EFS, PFS, OS
Event free survival
PFS from registration
Arm 1st randomisation
Arm 1st randomisation
100
100
e
75
75
gta
tage
n
n
erce
erce
50
ep
50
ep
tiv
tiv
la
la
u
u
m
m
u
u
C
25
C
25
N
F
N
F
MP+T
MP
168 159
MP+T
MP
168 146
MP+T
165 130
MP+T
165 124
MP
Logrank P <.001
MP
Logrank P =.02
0
0
0
12
24
36
months 48
0
12
24
36
months 48
At risk:
At risk:
MP 168
57
12
3
0
MP 168
92
26
6
1
MP+T 165
85
36
13
3
MP+T 165
94
40
15
4
Overall survival
Arm 1st randomisation
100
75
getan
erce
50
eptivla
MP+T
umu
MP
C
25
N
F
MP
168 95
MP+T
165 78
Logrank P =.16
0
0
12
24
36
months 48
Weijermans et al. ASH 2008 (abstract )
At risk:
MP 168
127
78
38
8
MP+T 165
120
84
41
14
HOVON 87/NMSG study for 1st line
treatment of the elderly with MM (2008-
y(
)
MP-Thalidomide
MP-Lenalidomide
vs
8 cycles
cycles
8 cycles
Randomization
cycles
evaluation
If PR/CR
Maintenance/
Thalidomide
Lenalidomide
50 mg/daily
10 mg/daily
Consolidation
Goals:
Endpoints:
- Ri
Rap d
id CR
CR
- PFS
- Disease control
-CR
Reduced dose Bortezomib in non-transplant
candidates vs
vs normal dose (Hajek
(Hajek et
et al)
al)
OS (from diagnosis)
OS (from start of therapy)
TTP
1.0
junior
1.0
junior
1.0
junior
0.9
senior
0.9
senior
0.9
senior
0.8
0.8
0.8
0.7
0.7
0.7
0.6
0.6
0.6
0.5
proportion
0.5
0.5
e
eproportion
veproportion
rviving
v
rviving
v
rviving
04
0.4
04
0.4
p=0.277
04
0.4
su
p=0.915
su
su
p=0.249
0.3
0.3
0.3
0.2
0.2
0.2
0.1
Cumulati
0.1
0.1
Cumulati
Cumulati
0.0
0.0
0.0
0
50
100
150
200
02468 10 12 14 16 18 20
02468 10 12 14 16 18 20
Time (months)
Time (months)
Time (months)
senior
junior
senior
junior
senior
junior
N
21
19
N
21
19
N
21
19
median
69.5
---
median
9.0
---
median
6.6
---
months
months
months
Maintenance trials in patients with
it
int
i
ens ve or no int
i
ens ve treatment
Myeloma IX Intensive pathway
Randomise
Bi
h
sp
h
osp onat
Clodronate
Zoledronate
te:
Clodronate
VS
Zoledr
VS
C-VAD
C-TD
VS
4-6 courses
4-6 courses
HDM200
Chemotherapy:
+
PBSCT (autograft)
Patients with potential sibling donors will also be offered an
LIC allogenei
e c Procedur
ocedu e (mini
(
all
a ogr
og af
a t)
t)
Randomise
Thalidomide
No Thalidomide
Maintenance:
VS
Myeloma IX Non-Intensive pathway
Randomise
Bisphosphonate:
Clodronate
Zoledronate
VS
MP
CTDa
Chemotherapy:
VS
Randomise
Thalidomide
No Thalidomide
Maintenance:
VS
OS by intensive and non-intensive pathway
Intensive pathway
maintenance
Median survival from
No maintenance
maintenance in intensive
pathway is >48 months
Median survival from
maintenance in non
intensive pathway is 36
Non-intensive pathway
intensive pathway is 36
py
months
No maintenance
There is no survival benefit
mainte
ma
na
inte
nc
na
e
There is no survival benefit
nc
for thalidomide
maintenance in either
pathway
Morgan et al. ASH 2008 (abstract )
Impact of maintenance on survival after
relapse in the intensive arm
PFS for PRs post intensive
Survival after relapse for PRs post
treatment
intensive treatment
PFS BY MAINTENANCE TREATMENT - INTENSIVE PATIENTS
PRs (POST INDUCTION RESPONSE) - INTENSIVE PATIENTS ONLY
maintenance
FOR PRs ONLY (POST INDUCTION RESPONSE)
SURVIVAL AFTER RELAPSE BY MAINTENANCE TREATMENT
100
100
2
maintenance = 9.19
2
1
= 7.28
1
P = .0024
P = .0070
80
80
60
60
GNIVIVR
D
U
E
S
SS 40
% 40
NO THAL N= 38
ER
E
G
VI
O
T
R
A
P
THAL N= 79
L
T
U
O
M
N
U
% 20
C 20
THAL N= 31
NO THAL N= 76
.5
1
1.5
2
2.5
3
3.5
4
4.5
.4
.8
1.2
1.6
2
2.4
2.8
TIME (YEARS)
TIME (YEARS)
Morgan et al. ASH 2008 (abstract )
Impact of maintenance on "14 Bad"
SURVIVAL IN 'BAD' 14 TRANSLOCATION GROUP BY MAINTENANCE
translocation
100
80
60
NO MAINT N= 32
GINVIVRUS% 40
Thalidomide maintenance
EVITA
2
MAINT N= 31
L
= .93
U
1
M
had no impact on the OS
U
P = .34
C 20
of patients with "14 Bad"
Bad
translocations
.5
1
1.5
2
2.5
3
3.5
4
4.5
TIME (YEARS)
SURVIVAL IN 'NORMAL' 14 TRANSLOCATIONS BY MAINTENANCE
100
80
NO MAINT N= 171
60
GN
MAINT N= 160
IVIVRUS% 40EVITA
2
L
= 2.68
U
1
MU
P = .1
C 20
.5
1
1.5
2
2.5
3
3.5
4
4.5
TIME (YEARS)
Morgan et al. ASH 2008 (abstract )
Survival after progression from
maintenance by 17p
yp-
SURVIVAL AFTER PROGRESSION BY MAINTENANCE RANDOMISATION
FOR PATIENTS WITH A 17p- ABNORMALITY
100
no thal N= 6
80
Maintenance with
2
60
= 5.32
1
G
P = .02
thalidomide in patients
NIVIVRUS 40
with 17p- is associated
%EVITA
thal N= 12
LU
with impaired survival after
MUC 20
maintenance
progression
.4
.8
1.2
1.6
2
2.4
TIME (YEARS)
Majority
jy of patients
p
die of
SURVIVAL AFTER PROGRESSION BY MAINTENANCE RANDOMISATION
FOR PATIENTS WITHOUT A 17p- ABNORMALITY
progressive disease
100
2 = .8
1
P = .37
80
Does this imply selection
no thal N= 76
60
selection
GNIV
of resistant clones???
IVRUS% 40EVITALUM
thal N= 61
UC 20
.5
1
1.5
2
2.5
3
TIME (YEARS)
Morgan et al. ASH 2008 (abstract )
Other trials
Ti
Tri l
a s in
l
re apse
t
pa i
tients
MERIT
Mye
y loma
e
and Renal Impairment
I
Trial
Trial (UK)
A randomised controlled trial of adjunctive plasma
exchange inpati
t
en
ith
sw
l
new y diagnosed
lti
mu
l
p e
myeloma and acute renal failure
PIs: G Gaskin and J Behrens
Does the addition of plasma exchange to
chemotherapy increase the rate of renal
recovery in patients presenting
presenting with acute
acute renal
failure and newly diagnosed multiple myeloma?
286 patients over
over 5 years recruited 100
Primary endpoint
Proportion of patients alive and dialysis-independent at
100 days
t
pos -randi
domisatition
GMMG-RELAPSE study
relapsed Multiple
pp
Myeloma
y
(1.-3. relapse)
p)
age 18-70 years
relapse 12 months after high dose therapy
Randomization
3x RD
3x RD
Cyclophosphamide + G-CSF
Cyclophosphamide + G-CSF
+ stem cell collection 1)
+ stem cell collection 1)
RD
HD Mel 200mg/m²
until progression/ relapse
+ autologous transplantation
R-maintenance 2)
until progression/ relapse
1) stem cell collection only if no useable stem cells are available from earlier mobilization
2) Lenalidomide (Revlimid®) maintenance therapy 10mg/day
R-Lenalidomide (Revlimid®), D-Dexamethasone, HD Mel-high dose Melphalan
HOVON 86 phase I/II study of weekly
Bortezomib + Lenalidomide in 1st relapse
Bortezomib 1.3-1.6, once weekly
Remission
Induction
Lenalidomide 10-20 mg daily
Dexamethasone
6-9 cycles
Maintenance/
Lenalidomide 10 mg daily
Consolidation
Endpoints:
Age 60-80
- CR / VGPR
1st relapse
- PFS, TTP
Thal treated or naive
Bendamustine Bortezomib - Dexamethason
for treatment of patients with relapsed or
refractory multiple myeloma (CEMSG)
Study Objectives
Primary:
sCR, CR, VGPR, PR, MR, SD, PD
Bendamustine 70mg/m2 d 1+4
Bortezomib 1.3mg/m2
g
d 1, 4, 8,
,,, 11
Dexamethasone 20mg d 1, 4, 8, 11
repeat every 4 weeks
ib
maximum number f
o cycles: 8
Intensive treatment at relapse - Myeloma X
UK : Non int
i
ens ve
l
re apse
Randomise
Rev/Dex
RCD
To maximum response
Randomise
Stop
Revlimid
treatment
maintenance
Acknowledgements
· CEMSG
· H. Ludwig, R. Hajeck et al
· DMSG
· H. Einsele, M Knop et al
· GMMG
· H. Goldschmidt et al
· HOVON
· H.M. Lokhorst, P. Weijermans, S. Zweegman et al
· NMSG
· P. Gimseng, U. Melquist, A. Waage et al
· UK MF
· G. Morgan et al