2011-05-05 Paris IFM 13.Int. Myeloma WS
C. Straka
13. International Myeloma Workshop
Paris, 05.05.2011
EMNTG DSMM Germany
Christian Straka
Berg, Germany
Age-adjusted high-dose melphalan in
elderly patients with multiple myeloma
PBSCs
PBSCs
IFM
Age 65-75 years
C
C
MEL
MEL
IFN
+
+
CY
GIMEMA
Age 51-70 years
Dex
Dex
100 2 Mo 100
PBSCs
PBSCs
DSMM II
Age 60-70 years
N = 216
C
C
C
C
Ø
A1
+
+
+
+
IEV
MEL
MEL
Dex
Dex
Dex
Dex
140
2 Mo
140
N = 434
R
PBSCs
PBSCs
A2
MEL
MEL
Ø
Dex IEV
N = 218
140
140
2 Mo
1
2011-05-05 Paris IFM 13.Int. Myeloma WS
C. Straka
DSMM II Non-hematological toxicity NCI-Grade 3/4
1. High-dose Melphalan 2. High-dose Melphalan
Induction
No Induction
Induction
No Induction
A1
A2
A1
A2
Infection
31 %
45 %
37 %
33 %
Oral
7 %
16 %
5 %
6 %
Mucositis
MEL 140 vs MPT vs VMP
Progression and treatment free survival (PTFS)
GIMEMA
IFM
DSMM II DSMM II
VISTA
Tandem-
Tandem-
MP-THAL
MP-THAL
VMP
MEL 140
MEL 140
Induction
No Induction
A1
A2
Median PFS
29 Months
28 Months
22 Months
20 Months
22 Months
Treatment
until
17 Months
7 Months
4 Months
13 Months
Time
progression
PTFS
15 Months
16 Months
OS at
80 %
68 %
75 %
69 %
69 %
3 years
OS Median
45 Months
52 Months
51 Months
52 Months
2
2011-05-05 Paris IFM 13.Int. Myeloma WS
C. Straka
GIMEMA: Newly diagnosed MM, 65-75 years,
intention-to-treat, n = 102
After tandem
After PAD
After LP-L
MEL100 + ASCT
CR
12 %
33 %
40 %
VGPR
55 %
76 %
78 %
PR
88 %
93 %
93 %
Median follow-up: 21 months
2-year PFS 69 %
2-year OS 86 %
Palumbo et al. J Clin Oncol 2010
ECOG-E4A03: RD or Rd +/- Transplant
Landmark analysis on patients surviving the first 4 cycles of therapy
65 years
> 65 years
Continued primary
Transplant
Continued primary
Transplant
RD or Rd > 4 cycles
group
RD or Rd > 4 cycles
group
n = 141
n = 68
n = 200
n = 22
1-year survival, %
94
100
94
95
2-year survival, %
88
94
81
91
3-year survival, %
78
94
69
83
Siegel DS et al. ASH 2010 Abstract #38
3
2011-05-05 Paris IFM 13.Int. Myeloma WS
C. Straka
DSMM XIII
2010
MM 60 75
PI: Ch. Straka
R
Randomization
A1
A2
R+low Dex
R + low Dex
Rd: Rev 25 mg d 1-21/28
Dex 40 mg d 1,8,15,22
R+low Dex
R + low Dex
R+low Dex
R + low Dex
Mobilization of PBSC
MOB
MOB
(G +/- chemo)
R+low Dex
MEL 140
with autologous PBSC
R+low Dex
R+low Dex
MEL 140
with autologous PBSC
R+low Dex
Revlimid
Rev 10 mg per day
maintenance
R+low Dex
until progression
until progression
DSMM XIII: Asked Questions
Is there a benefit of age-adjusted high-dose
melphalan (140 mg/m²) with autologous blood stem
cell transplantation during first-line therapy with novel
agents (lenalidomide) in elderly myeloma patients
(60-75 years) ?
Comparison of first-line vs. second-line age-adjusted
high-dose melphalan with autologous transplantation
4
2011-05-05 Paris IFM 13.Int. Myeloma WS
C. Straka
DSMM XIII
2010
MM 60 75
PI: Ch. Straka
Inclusion:
Age 60 75 years
Symptomatic multiple myeloma (CRAB)
Measurable disease
ECOG performance status 2
Exclusion:
Renal failure requiring dialysis
Antithrombotic prophylaxis not possible
Prior chemotherapy (except short-course Dex)
Prior Dex toxicity grade 3
Stratification at randomization:
ISS stage I + II versus stage III
Age 70 years versus > 70 years
Primary end point / statistics:
Progression-free survival (PFS)
10 months difference in PFS, A2 > A1 350 patients
DSMM XIII
Status: April 28, 2011
Centers:
Central Cytogenetics:
Planned:
35
+9q34
66%
Initiated:
26
del 13q14
26%
+1q21.2
20%
Patients:
t(4;14)
4%
del 17p13
0
Randomized: 69
t(14;16)
0
5
2011-05-05 Paris IFM 13.Int. Myeloma WS
C. Straka
dsmm
centers
· kiel
· greifswald
Chairmen
· rostock
· lübeck
Hermann Einsele, Würzburg
· hamburg
Christian Straka, Berg
· oldenburg
· bremen
· berlin
Participating Centers
·
·
potsdam
hannover
> 50 in Germany
· münster
· braunschweig
· magdeburg
·
· goslar
·
·
göttingen
cottbus
duisburg · dortmund
· halle
Central Cytogenetics, Ulm
· essen
· leipzig · dresden
·
Christian Langer
·
eisenach
bad hersfeld
·
·
erfurt
köln
· bad friedrichshall
Peter Liebisch
· idar-oberstein
· frankfurt
· wiesbaden
Statistics
· trier
· mainz
· kaiserslautern
·
Axel Hinke, Langenfeld
·
würzburg
homburg
· saarbrücken
· erlangen
· nürnberg
· karlsruhe · ludwigsburg
· regensburg
· stuttgart
· schwäbisch gmünd
CRO ClinAssess, Leverkusen
· tübingen
· ulm · augsburg
Burkhard Deuß
· villingen-schwenningen
· offenburg
· münchen
· freiburg
· berg
Anja Liebert
· kempten
Marianne Sauerwein
6