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Hans Salwender, MD
Treatment of Younger Myeloma Patients
Induction Therapy
Disclosure of Potential Conflicts of Interest: Honoraria and Consultant
Celgene Binding site
Mundipharma Chugai Pharma
Janssen Cilag
Novartis
Asklepios Klinik Altona, Hamburg, Germany
Sylt Bad Griesbach Barmbek (Hamburg) Falkenstein Ini Hannover
Treatment of Younger Myeloma Patients
Induction Therapy
Hans Salwender, MD
Head of Department of Hematology
Stemcell transplant unit
Asklepios Klinik Altona
Hamburg, Germany
Altona (Hamburg)
Induction of what and when?
MGUS, SMM, symptomatic MM
Barlogie et al., BrJH 2006
IMWG recommendations for global myeloma care
PARAMETERS FOR THE INITIATION OF THERAPY
Treatment should be initiated in all p. with active myeloma fulfilling the CRAB criteria,
…one or more of clinically relevant bone lesions, anemia (Hb 10 g/dl), myeloma induced renal
impairment (creatinine 2.0 mg/ml) and hypercalcemia (11.0 mg/dl),
as well as in those symptomatic owing to the underlying disease.
…
…before results have been confirmed by other trials, starting treatment when patients
become symptomatic because of myeloma and/or fulfill the CRAB criteria is considered
standard,
although initiation of therapy may also be considered for prevention of
imminent disease-related complications such as increasing deterioration of renal
function, but not having reached the cutoff level of 2 mg/dl creatinine.
Ludwig H et al., Leukemia. 2013 Oct 9
Smoldering Myeloma
Dispenzieri A et al, Blood 21. Oct 2013
Survival of patients with renal failure
according to induction treatment (VAD vs. PAD)
Scheid C et al., Haematologica 2014, 99(1)
PFS
OS
Association between response and OS in
patients with newly diagnosed MM treated with HDT
IFM90 CR/VGPR vs. PR vs. Other <0.00001
MRC VII CR vs. PR vs. MR 0.00002
TT1 CR vs. PR 0.2496
TT2 CR vs. PR/NR <0.05
IFM94-02 Maximal response <0.001
IFM99C CR/VGPR vs. PR <0.0000
NMSG 5/94 CR vs. PR/NR 0.38
Bologna VGPR or better vs. Other 0.002
GMA CR/MRD vs. Other 0.22
Combined <0.00001
Modified. Van de Velde et al., Haematologica 2007; 92:1399-1406.
CR/VGPR enough?
Martinez-Lopez J et al., BLOOD, 21 JULY 2011, VOLUME 118
EMN-Recommendations
Modified. Engelhardt M et al., Haematologica 2014, 99(2)
Sonneveld P et al., J Clin Oncol. 2013 Sep 10;31(26):3279-87
Bortezomib-Based Versus Nonbortezomib-Based Induction
Treatment Before Autologous Stem-Cell Transplantation in
Patients With Previously Untreated Multiple Myeloma:
A Meta-Analysis of Phase III Randomized, Controlled Trials
Bortezomib-based induction treatment
Modified. Sonneveld P et al., J Clin Oncol. 2013 Sep 10;31(26):3279-87
Postinduction response rate
Sonneveld P et al., J Clin Oncol. 2013 Sep 10;31(26):3279-87
Post-transplantation CR plus nCR-rate
Subgroup analysis
Sonneveld P et al., J Clin Oncol. 2013 Sep 10;31(26):3279-87
Progression-free survival
Median follow up 37 months
Impact of bortezomib on outcome in pts with
high-risk cytogenetics: Results from 3 European trials
Vel-based regimens Non Vel-based
regimens
P
Post-induction CR rate
Overall
Pts with high-risk cytogen.
14.5%
18.6%
4%
0.6%
< 0.001
< 0.001
Median PFS
Overall
Pts with high-risk cytogen.
Pts without high-risk cytogen.
Pts with t(4;14), but no del17p
Pts with del17p, but no t(4;14)
41.5 mos
32 mos
47 mos
36 mos
27 mos
33 mos
22 mos
38 mos
24 mos
19 mos
< 0.001
< 0.001
0.01
0.001
0.014
• Multivariate analysis: independent variables associated with extended PFS: lack of high-risk
cytogen., thrombocytopenia, high β2-M, anemia, achievement of CR after induction therapy
• Vel-based ASCT not associated with prolonged PFS in pts with both t(4;14) and del(17p)
(ultra high-risk): they had shortest PFS (median: 21 mos); multivariate analysis showed
benefit from double ASCT
Cavo et al. ASH 2012 (Abstract 749), oral presentation
Impact of bortezomib on outcome in pts with
high-risk cytogenetics: Results from 3 European trials
Vel-based regimens Non Vel-based
regimens
P
Median OS
Overall Trend favoring incorporation of Vel 0.58
Pts with high-risk cytogenetics 65 mos 41 mos 0.004
• Conclusion
• Higher CR rates and extended PFS with Vel-based regimens
• PFS benefit retained across pts with and without high-risk cytogenetics
• Vel-based ASCT significantly improved outcome of pts with high-risk cytogenetics,
but did not overcome the adverse prognosis imparted by t(4;14) and/or del(17p)
Cavo et al. ASH 2012 (Abstract 749), oral presentation
GMMG-HD4 / HOVON65 -trial
Cooperative trial by the Dutch-Belgium HOVON Myeloma Working Party & the German-speaking Myeloma Multicenter Group GMMG based on a common protocol, study rules, datamanagement, monitoring and analysis.
Accrual period 05/2005 – 06/2008, 835 patients
Presented data based on 835 patients (827 eligible) per final analysis of 20 November 2013.
Median follow-up of 490 patients alive is 74 months
Bortezomib-based treatment consistently improves PFS (median 27 m vs 36 m) and OS (median 84 m vs not reached, p=0.05) in patients with newly diagnosed MM who are transplant eligible
Sonneveld P et al. ASH 2013 abstract 404
Randomization
NDMM, age 18–65 y
CAD + GCSF
3 x VAD
CAD + GCSF
3 x PAD
MEL 200 + PBSCT
In GMMG 2nd
MEL 200 + PBSCT
MEL 200 + PBSCT
In GMMG 2nd
MEL 200 + PBSCT
Thalidomide
maintenance
50 mg/day for
2 years
Bortezomib
Maintenance
1.3 mg/m2 / 2 weeks
for 2 years
Bortezomib 1.3 mg/m2
i.v.
Doxorubicin 9 mg/m2
Dexameth 40 mg
GMMG-HD4 / HOVON65 -trial
Modified. Sonneveld P et al. ASH 2013 abstract 404
Survival of patients with renal failure
according to induction treatment (VAD vs. PAD)
Scheid C et al., Haematologica 2014, 99(1)
GMMG-HD4 / HOVON65 -trial IR and HR groups compared to good risk per treatment arm
Arm Relative risk P value
VAD IR HR 2.26,
CI 1.42-3.58
<0.001
HR HR 5.02,
CI 2.89-8.73
< 0.001
PAD IR HR 1.26
CI 0.82-1.92
0.29
HR HR 2.04
CI 1.20-3.48
0.009
PFS
Sonneveld P et al. ASH 2013 abstract 404
GMMG MM5 Trial In Newly Diagnosed Multiple Myeloma To Evaluate
PAd Vs VCD Induction Prior To High Dose Treatment Followed By
Lenalidomide Consolidation and Maintenance –
Final Analysis On Induction Therapy Hartmut Goldschmidt, MD, Jan Duerig, MD, Uta Bertsch, MD, Christina Kunz, PhD, Thomas
Hielscher, Mathias Haenel, MD, Igor Wolfgang Blau, MD, PhD, Dirk Hose, Dr. med. dipl.-phys.,
Anna Jauch, PhD, Baerbel Schurich, PhD, Kai Neben, MD, Anja Seckinger, MD, Barbara Huegle-
Doerr, PhD, Maximilian Merz, MD, Markus Munder, MD, Walter Lindemann, MD, Matthias Zeis,
MD, Christian Gerecke, MD, Ingo GH Schmidt-Wolf, MD, Katja Weisel, MD, Christof Scheid, MD and
Hans Salwender, MD
n: 502
PAd VCD
≥ VGPR: 34.3% 37.0%
SAEs during induction 32.7% 24.0% p=0.037
Neutropenia 3°/4° 11.3% 35.2% p<0.001
Infections during induction 24.6% 22.4% p=0.60
No. of deaths 6 /251 1/ 251
Goldschmidt H, et al., abstract 3369, ASH 2013
PAd vs VCD Induction
Future ??
Carfilzomib, Lenalidomide, and Dexamethasone Followed By Lenalidomide Extended
Dosing (CRd – R) In High Risk Smoldering MM Pat
8 Zyklen Carfilzomib 20/36mg, Lenalidomide 25, Dex 20/10 --- 24 Zyklen Len 10
Response nach 8 Zyklen CRd: 12/12 Pat mit nCR/CR/sCR, 11/12 MRD neg.
Landgren et al. abstract 1939, ASH 2013
Induction Therapy, Younger Myeloma Patients
Conclusions:
- Start treatment before the onset of severe renal impairment
- Bortezomib significantly improves the long-term outcome
of patients presenting with renal failure
- Bortezomib improves outcome in patients with
intermediate/poor risk based on FISH/ISS
Questions?
RD vs RCD vs VCD
Khan et al., British Journal of Haematology, 156, 326–333, 2011
Richardson et al., Blood, 5 August 2010, Vol 116, No 5
Double Vs Single Autologous Stem Cell Transplantation After Bortezomib-Based
Induction Regimens For Multiple Myeloma: An Integrated Analysis Of Patient-Level
Data From European Phase III Studies
Michele Cavo, MD, Hans Salwender, MD, Laura Rosiñol, MD, Philippe Moreau, MD, Maria Teresa Petrucci,
MD, Igor Wolgang Blau, MD, Joan Bladé, MD, PhD, Michel Attal, MD, Francesca Patriarca, MD, Katja Weisel,
MD, Jesus F San Miguel, MD, PhD, Herve Avet-Loiseau, MD, Nicoletta Testoni, BS, Michael Pfreundschuh,
Prof MD, Juan Jose Lahuerta, MD, Thierry Facon, MD, Lucia Pantani, MD, Christof Scheid, MD, Norma
Gutierrez, PhD, MD, Gerald Marit, MD, Antonio Palumbo, MD, Maria Luisa Martin, PhD, Denis Caillot, MD and
Hartmut Goldschmidt, MD
Cavo M et al., abstract 767, ASH 2013
CR after induction in high-risk patients
Smoldering Myeloma
Lenalidomide plus Dexamethasone for High-Risk Smoldering MM
Mateos et al., N Engl J Med 2013; 369:438-447; August 1, 2013
“3-year survival rate was higher in the treatment group (94% vs. 80%; P=0.03).”
CR necessary after induction?
No:
Singhal S et al.:
Response to induction chemotherapy is not essential to obtain survival benefit
from high-dose melphalan and autotransplantationin myeloma.
Br J Haematol. 2002;30(10):673-679.
Yes:
Alvares CL et al.
Longterm outcomes of previously untreated myeloma patients: response to
induction chemotherapy and high-dose melphalan incorporated within a
risk stratification model can help to direct the use of novel treatments.
Br J Haematol. 2005;129(5):607-614.
Impact of bortezomib on outcome in pts with high-
risk cytogenetics: Results from 3 European trials
• Study details:
– Integrated analysis of 4 phase 3 studies conducted by
HOVON/GMMG, IFM, PETHEMA/GEM, GIMEMA:
• Comparison of
– Bortezomib-based (Vel-based) induction regimens (VD or
VTD or PAD)
– vs non bortezomib-based (non Vel-based) treatments (VAD or
TD) before single or double ASCT for newly diagnosed MM
• Analysis of impact of bortezomib in post-ASCT consolidation or
maintenance therapy in 3 trials
– 2169 pts enrolled, data on cytogenetics available for 1894 pts
– Pts followed for median 37 months
Cavo et al. ASH 2012 (Abstract 749), oral presentation
Impact of bortezomib on outcome in pts with high-
risk cytogenetics: Results from 3 European trials
Vel-based
regimens
Non Vel-based
regimens
P
Post-induction CR rate
Overall
Pts with high-risk cytogen.
14.5%
18.6%
4%
0.6%
< 0.001
< 0.001
Median PFS
Overall
Pts with high-risk cytogen.
Pts without high-risk cytogen.
Pts with t(4;14), but no del17p
Pts with del17p, but no t(4;14)
41.5 mos
32 mos
47 mos
36 mos
27 mos
33 mos
22 mos
38 mos
24 mos
19 mos
< 0.001
< 0.001
0.01
0.001
0.014
• Multivariate analysis: independent variables associated with extended PFS: lack of
high-risk cytogen., thrombocytopenia, high β2-M, anemia, achievement of CR after
induction therapy
• Vel-based ASCT not associated with prolonged PFS in pts with both t(4;14) and
del(17p) (ultra high-risk): they had shortest PFS (median: 21 mos); multivariate
analysis showed benefit from double ASCT
Cavo et al. ASH 2012 (Abstract 749), oral presentation
Impact of bortezomib on outcome in pts with high-
risk cytogenetics: Results from 3 European trials
Vel-based
regimens
Non Vel-based
regimens
P
Median OS
Overall Trend favoring incorporation of Vel 0.58
Pts with high-risk cytogenetics 65 mos 41 mos 0.004
• Double ASCT favorably influenced OS in pts with both high-risk cytogenetics
and ultra high-risk cytogenetics
• Conclusion
• Higher CR rates and extended PFS with Vel-based regimens
• PFS benefit retained across pts with and without high-risk cytogenetics
• Vel-based ASCT significantly improved outcome of pts with high-risk
cytogenetics, but did not overcome the adverse prognosis imparted by
t(4;14) and/or del(17p)
Cavo et al. ASH 2012 (Abstract 749), oral presentation
Impact of bortezomib on outcome in pts with high-
risk cytogenetics: Results from European trials
Vel-based
regimens
Non Vel-based
regimens
P
Post-induction CR rate
Overall
Pts with high-risk cytogen.
14.5%
18.6%
4%
0.6%
< 0.001
< 0.001
Median PFS
Overall
Pts with high-risk cytogen.
Pts without high-risk cytogen.
Pts with t(4;14), but no del17p
Pts with del17p, but no t(4;14)
41.5 mos
32 mos
47 mos
36 mos
27 mos
33 mos
22 mos
38 mos
24 mos
19 mos
< 0.001
< 0.001
0.01
0.001
0.014
• Vel-based ASCT not associated with prolonged PFS in pts with both t(4;14) and
del(17p) (ultra high-risk): they had shortest PFS (median: 21 mos)
• Double ASCT favorably influenced OS in pts with both high-risk cytogenetics and
ultra high-risk cytogenetics
Cavo et al. ASH 2012 (Abstract 749), oral presentation
# 404 - Bortezomib Induction and Maintenance Treatment Improves Survival In
Patients With Newly Diagnosed Multiple Myeloma: Extended Follow-Up Of The
HOVON-65/GMMG-HD4 Trial Sonneveld et al.
# 767 - Double Vs Single Autologous Stem Cell Transplantation After Bortezomib-
Based Induction Regimens For Multiple Myeloma: An Integrated Analysis Of Patient-
Level Data From Phase European III Studies Cavo et al.
# 3369 - GMMG MM5 Trial In Newly Diagnosed Multiple Myeloma To Evaluate PAd Vs
VCD Induction Prior To High Dose Treatment Followed By Lenalidomide Consolidation
and Maintenance – Final Analysis On Induction Therapy Goldschmidt et al.
HOVON-65/GMMG-HD4 Trial Conclusion
Bortezomib-based treatment improves PFS (median 27 months vs 36 months) and OS (median 84 months vs not reached, p=0.05)
Bortezomib significantly improves long-term outcome of pts with renal failure (P<0.001)
Double ASCT improves PFS and OS in pts with ISS1
Bortezomib improves outcome in pts with intermediate/poor risk disease
No increased risk of SPM
Sonneveld et al. ASH 2013 #404
CR plus nCR rate post-transplantation
Sonneveld et al, J Clin Oncol, 2013
Post-transplantation CR/nCR rate
by patients subgroup
Sonneveld et al., J Clin Oncol, 2013
Progression-free survival
Sonneveld et al, J Clin Oncol, 2013
PFS, for the individual studies
Sonneveld et al, J Clin Oncol, 2013
HOVONGMMGCox LR P =0.02
N140148
D5233
HOVONGMMG
At risk:140148
136139
127131
115120
106113
8588
4453
1817
HOVON
GMMG
0
25
50
75
100
months0 12 24 36 48 60 72 84
Cum
ula
tive p
erc
enta
ge
HOVONGMMGCox LR P =0.50
N9791
D5749
HOVONGMMG
At risk:9791
7674
5967
5155
4848
4035
2011
62
HOVON
GMMG
0
25
50
75
100
months0 12 24 36 48 60 72 84
Cum
ula
tive p
erc
enta
ge
HOVONGMMGCox LR P =0.50
N9791
D5749
HOVONGMMG
At risk:9791
7674
5967
5155
4848
4035
2011
62
HOVON
GMMG
0
25
50
75
100
months0 12 24 36 48 60 72 84
Cum
ula
tive p
erc
enta
ge
ISS 3
ISS 2 ISS 1
OS by ISS group:
single (HOVON) vs double (GMMG) transplant
P=0.02 NS
NS
Sonneveld et al. ASH 2013 #404
F27139
26023
N36845
37636
VAD, BLC<2VAD, BLC>2PAD, BLC<2PAD, BLC>2
VAD, BLC<2
VAD, BLC>2
PAD, BLC<2
PAD, BLC>2
0
25
50
75
100
months0 12 24 36 48 60 72 84
Cum
ula
tive p
erc
enta
ge
Survival of patients with renal failure
by treatment arm
VAD, BLC<2VAD, BLC>2PAD, BLC<2PAD, BLC>2
N36845
37636
D15935
14916
VAD, BLC<2
VAD, BLC>2
PAD, BLC<2
PAD, BLC>2
0
25
50
75
100
months0 12 24 36 48 60 72 84
Cum
ula
tive p
erc
enta
ge
PFS OS
HR=0.44, CI 0.26-0.75 P=.003 HR=0.38, CI 0.21-0.69, P<.001
Sonneveld et al. ASH 2013 #404
Survival of patients with renal failure
by treatment arm
VAD, BLC<2VAD, BLC>2PAD, BLC<2PAD, BLC>2
N36845
37636
D15935
14916
VAD, BLC<2
VAD, BLC>2
PAD, BLC<2
PAD, BLC>2
0
25
50
75
100
months0 12 24 36 48 60 72 84
Cum
ula
tive p
erc
enta
ge
OS
HR=0.38, CI 0.21-0.69, P<.001
Sonneveld et al. ASH 2013 #404
A: VADB: PADLogrank P =0.16
N270230
F215170
A: VADB: PAD
At risk:270230
203188
148128
10589
6963
3639
1215
37
A: VADB: PAD
0
25
50
75
100
months0 12 24 36 48 60 72 84
Cum
ula
tive p
erc
enta
ge
A: VADB: PADLogrank P =0.05
N270230
D10874
A: VADB: PAD
At risk:270230
255220
226203
197190
172162
100106
4642
87
A: VAD
B: PAD
0
25
50
75
100
months0 12 24 36 48 60 72 84
Cum
ula
tive p
erc
enta
ge
Progression-free and overall survival
from start of maintenance
PFS OS
P= NS HR=0.71, CI 0.52-0.98, p=0.035
Conclusions (2)
• Double HDT and ASCT improves PFS
and OS in patients with ISS 1 NDMM in
the era of novel agents
• Bortezomib improves outcome in patients
with intermediate/poor risk based on
FISH/ISS
• No increased risk of SPMs was observed
Conclusions (1)
• Bortezomib-based treatment consistently
improves PFS (median 27 m vs 36 m)
and OS (median 84 m vs not reached,
p=0.05) in patients with newly diagnosed
MM who are transplant eligible
• Bortezomib significantly improves the
long-term outcome of patients presenting
with renal failure (p<0.001)
Progression-free survival with censoring
at allo-SCT: primary endpoint
A: VADB: PADCox LR Stratified
N373371
F225197
P =0.005
A: VADB: PAD
10 Nov 2010-15:13:13
At risk:373371
258295
176218
97
112
2636
A: VAD
B: PAD
0
25
50
75
100
months0 12 24 36 48
Cum
ulat
ive
perc
enta
ge
PFS with censoring at allo-SCT
HR = 0.75 (0.62-0.91), P=0.004
P. Sonneveld et al., JCO 2012
PFS (allo censored) OS
t HR p t HR p
Arm 0.74 .002 Arm 0.70 .013
WHO 1.22 .005 WHO 1.49 <.001
IgA 1.62 .002 IgA 1.82 .01
IgG 1.33 .041 IgG 1.71 .008
LDH 1.25 .10 LDH 1.59 .006
ISS 1.25 .001 ISS 1.47 <.001
13q- 1.43 .001 13q- 1.62 .002
SG 0.81 .039 SG 0.73 .031
Multivariate Cox regression analysis
P. Sonneveld et al., JCO 2012
PFS in IR and HR groups compared to
good risk per treatment arm
Arm Relative risk P value
VAD IR HR 2.26,
CI 1.42-3.58
<0.001
HR HR 5.02,
CI 2.89-8.73
< 0.001
PAD IR HR 1.26
CI 0.82-1.92
0.29
HR HR 2.04
CI 1.20-3.48
0.009
Sonneveld et al. ASH 2013 #404
ISS 3, high LDH and t(4;14) and/or del(17p) as a
prognostic index for OS
• Validation of scoring system in large data set:
– GIMEMA (VTD vs TD) 474 pts
– PETHEMA/GEM (VTD vs TD vs VBMCP/VBAD/Vel) 386 pts
– HOVON/GMMG (PAD vs VAD) 827 pts
– IFM (VD vs VAD) 482 pts
– Total 2169 pts
– Data for risk factors available for 1601 pts
• 21% ISS 3, 20% t(4;14) and/or del17p, 60% LDH > normal
Score % of pts (n=1601) Outcome: 2-year OS
0 56% 93%
1 32% 85%
2 4% 67%
3 7% 55%
Moreau et al. ASH 2012 (Abstract 598), oral presentation
ISS 3, high LDH and t(4;14) and/or del(17p) as a
prognostic index for OS
Score Definition % of overall
population Outcome
0
Absence of adverse factors (neither
high LDH, nor ISS 3, nor t(4;14) and
/or del(17p))
57% 3-year OS: 89%
1
Presence of only 1 adverse factor
(either high LDH or ISS 3 or t(4;14)
and/or del(17p))
32% 3-year OS: 73%
2
Presence of high LDH plus ISS 3 in
the absence of t(4;14) and /or
del(17p)
6% 3-year OS: 68%
3 Presence of t(4;14) and/or del(17p) in
addition to either ISS 3 or high LDH 5%
Median OS:
19 mos
3-year OS: 24%
Moreau et al. ASH 2012 (Abstract 598), oral presentation
ISS 3, high LDH and t(4;14) and/or del(17p) as a
prognostic index for OS
• Study details: investigation of prognostic parameters of pts enrolled in
the IFM2005-01 trial
• Results
– Multivariate logistic regression analysis: risk of death from PD
within 2 years from start of therapy related to:
• high LDH > normal value (p = 0.0014)
• ISS 3 (p = 0.0097)
• cytogenetic abnormalities (= presence of either t(4;14) or 17p
deletion (p = 0.0002))
– Development of scoring system
– Identification of small group of pts with very high-risk disease
and a shortened survival despite use of intensive novel agent-
based therapy
Moreau et al. ASH 2012 (Abstract 598), oral presentation
Mateos M et al. NEJM 2013
Landgren et al. ASH abstract #1939, poster
8 Zyklen Carfilzomib 20/36 mg/m2 + Len/Dex, anschl. 24 Zyklen Len 10 mg/d
MM-003: OS by Cytogenetic Profile
Median OS
Standard Risk (n = 148) 14.0 mos
del(17p)/t(4;14) (n = 77) 9.9 mos
OS (mos)
Pro
po
rtio
n o
f P
ati
en
ts
0.2
0.4
0.6
0.8
1.0
0.0 4 8 12 16 20 24 0 28
del(17p)/t(4;14) vs. Standard Risk
P = .041
Dimopoulos et al. ASH 2013 # 408
IFM 94 IFM 90 Attal et al., N Engl J Med 2003 Attal et al., N Engl J Med 1996
Stellenwert von Hochdosistherapie und
Transplantationen beim Multiplen Myelom
Rev/dex vs Rev/DEX for newly diagnosed MM
Rajkumar et al.Lancet Oncol 2010; 11: 29–37
Sonneveld et al.,J Clin Oncol. 2013 Sep 10;31(26):3279-87
After follow up of 37 months 24% of patients died
Median OS had not been reached in either group
There was a significant improvement in OS in the bortezomib-based
induction group (HR, 0.81; 95% CI, 0.66 to 0.99; P .0402)
3-year OS rates were 79.7% and 74.7%, respectively
Bortezomib-Based Versus Non-Bortezomib-Based
Induction Treatment Before Autologous Stem-Cell Transplantation
Sonneveld et al.,J Clin Oncol. 2013 Sep 10;31(26):3279-87
Randomization
NDMM, age 18–65 y
CAD + GCSF
3 x VAD
CAD + GCSF
3 x PAD
MEL 200 + PBSCT
In GMMG 2nd
MEL 200 + PBSCT
MEL 200 + PBSCT
In GMMG 2nd
MEL 200 + PBSCT
Thalidomide
maintenance
50 mg/day for
2 years
Bortezomib
Maintenance
1.3 mg/m2 / 2 weeks
for 2 years
Trial design
Bortezomib 1.3 mg/m2
i.v.
Doxorubicin 9 mg/m2
Dexameth 40 mg
Sonneveld et al. ASH 2013 #404
Symptomatic MM. CR necessary for OS?