Induction with Ve
V lcade®/Dex
e
partially
overcomes the poor prognosis of t(4;14),
but nott
t h
that ofd
f d l
e (17
l(17 )
p
Hervé AVETLOISEAU, MD,PhD
Center for Research in Myeloma
University Hospital
Nantes, France
t(4;14) with VAD induction + HDMEL
B
p=10-12
Impact of t(4;14) on EFS
B
p=2.10-8
Impact of t(4;14) on OS
Avet-Loiseau et al., Blood 2007;109:3489
Gertz et al., Blood 2005;106:2837
t(4;14) with Velcade®
VISTA:
VIST
MP vs VMP
26 patients
TTP
OS
VMP standard risk
VMP standard risk
VMP high risk
VMP high risk
VMP standard risk (N=142): 23.1 months (34 events)
VMP standard risk (N=142): not reached (16 events)
VMP high risk (N=26): 19.8 months (7 events)
VMP high risk (N=26): not reached (3 events)
HR = 1.297 (95% CI: 0.55, 3.06)
HR = 1.009 (95% CI: 0.278, 3.663)
San Miguel et al., NEJM 2008;359:906
t(4;14) with Velcade®
Analysis of patients treated
tr
within
within, or
or according
according to
to,
the IFM 2005-01 trial
4 cycles
cycles of
of Vel/Dex
Vel/Dex (1.3 mg/m˛
mg/m˛, J1, J4, J8, J11)
J1
1 or 2 MEL200, according to response
t(4;14) with Velcade®
EFS of 507 patients treated with Vel/Dex induction
t(4 ;14)
0
> 0
pvalue
(logrank)
Pt
Pa i
ti
t
en s
396
106
t(4;14) neg
Relapses
141
43
0.0178
t(4;
(;14) pos
p
Median EFS
29
2. 0
90
23
2. 2
32
(years) [IC 95%]
[2.74 ;
[1.49 ;
3.53]
2.95]
p=.02
t(4;14) with Velcade®
OS of 507 patients treated with Vel/Dex induction
t(4;14) neg
t(4 ;14)
neg
pos
pvalue
(logrank)
t(4;14) pos
Pt
Pa i
ti
t
en s
400
107
Deaths
38
20
0.0020
p=
p .002
.002
Median OS
---*
---*
(years) [IC 95%]
[---* ; ---*]
[3.60 ; ---
*]
t(4;14) with Velcade®
Role of inclusion in the 2005-02 trial on EFS
(maintenance lenalidomide vs placebo)
inclusion 05-02
no
yes
pvalue
2005-02
(logrank)
t(4;14) patients
82
24
Relapses
37
6
0.0011
p=.001
Median EFS (years)
1.70
---*
[IC 95%]
[1.34 ; 2.35]
[2.42 ; ---*]
No maintenance
t(4;14) with Velcade®
Role of inclusion in the 2005-02 trial on OS
(maintenance lenalidomide vs placebo)
2005-02
inclusion 05-02
no
yes
pvalue
(logrank)
t(4;14) patients
83
24
Ni
No maintenance
Deaths
17
3
0.0758
Median OS
---*
---*
p=.07
(years) [IC 95%]
[2.96 ; ---
[---* ; ---
*]
*]
t(4;14) with Velcade®
Comparaison VAD vs Vel/Dex for t(4;14) on EFS
treatment
VAD
Vel/Dex
pvalue
()
(logrank)
Patients
98
106
Relapses
82
43
0.0006
Vel/Dex
Median EFS
1.36
2.32
p=.0006
(years) [IC 95%]
[1.08 ;
[1.49 ;
1.56]
2.95]
p=
p .0006
.0006
VAD
t(4;14) with Velcade®
Comparaison VAD vs Vel/Dex for t(4;14) on OS
treatment
VAD
Vel/Dex
pvalue
(logrank)
Vel/Dex
Patients
106
107
Dt
Dea h
ths
70
20
0.0004
Median OS (years)
2.87
---*
VAD
[IC 95%]
[1.76 ; 3.48]
[3.60 ; ---*]
p=.0004
Del(17p) with Velcade®
EFS of 525 patients treated with Vel/Dex induction
Del(17p)
57%
> 57%
pvalue
(logrank)
Patients
475
50
Relapses
166
30
< 0.0001
No del(17p)
Median EFS
2.95
1.17
(years) [IC 95%]
[2.75 ;
[0.72 ;
3.71]
20
2. 1]
01]
p<.0001
Del(17p) pos
Del(17p) with Velcade®
OS of 531 patients treated with Vel/Dex induction
No del(17p)
Del(17p)
57%
> 57%
pvalue
(logrank)
Patients
480
51
Deaths
48
15
< 0.0001
p<.0001
Median OS (years)
---*
4.07
[IC 95%]
[---* ; ---*]
[3.10 ; ---
*]
Del(17p) pos
Del(17p) with Velcade®
Comparaison VAD vs Vel/Dex for del(17p) on EFS
treatment
VAD
VA
V l/D
e
ex
pvalue
(logrank)
Patients
101
50
Relapses
82
30
0.3156
Median EFS
1.47
1.17
Vel/Dex
VAD
(years) [IC 95%]
[1.17 ;
[0.72 ;
1.83]
2.01]
p=.32
Del(17p) with Velcade®
Comparaison VAD vs Vel/Dex for del(17p) on OS
treatment
VAD
Vel/Dex
pvalue
(logrank)
Patients
115
51
Vel/Dex
0.4857
Deaths
70
15
VAD
Median OS (years)
2.40
4.07
[IC 95%]
[1.83 ; 3.66]
[3.10 ; ---*]
p= 49
.
t(4;14) with Velcade®
Conclusion
t(4;14) and del(17p) remain prognostic parameters with VD
Vel/Dex is not superior to VAD for del(17p) patients
Vel/Dex is superior to VAD for t(4;14) patients
Differences with VISTA & UAMS: Vel duration (?)
Acknowledgments