Upfront Bortezomib in Patients with
Higher than Average Risk Myeloma
December 7, 2008
Angela Dispenzieri, M.D.
Mayo Clinic
Scottsdale, Arizona
Rochester,
Rochester Minnesota
Jacksonville, Florida
E2A02 Schema
"Induction"
1 ineligible
N=44
Bortez* for 8 cycles
on days 1, 4, 8, & 11
If Progression after 2
(21 day cycle)
cycles, Off study
study
Option for PBSC
harvest after cycle
y
4
"Maintenance"
Bortez* days 1 & 15
(28 day cycle)
N=15
If progression, go
N=7
back to "Induction"
treatment schedule
Response Rates
Rates in Evaluable
Patients
70
60
13
13
6
50
17
40
patients
MR
PR
aluable
VGPR
30
eva
VG
44
44
42
20
sponding,
re
33
%
10
5
6
6
0
Total
Del 13
PCLI1.0
B2M5.5
N=38
N=6
N=16
N=31
There were n=27 patients with worst degree
pg
toxicity of Grade 3, n=6 patients
p
with
worst degree toxicity of Grade 4 and n=1 patient with Grade 5 toxicity (heart block
asystole).
Hemoglobin
He
63
28
Platelets
58
14
5
Fatigue
56
14
2
Neutrophils
40
16
16
Neuropathy
58
5
Neuropathic pain,
Motor,
Grade 3, 3%
Grade 1-2, 9%
Leukocytes
42
21
Grades 1-2
Neuropathic pain,
Grade 1-2, 17%
Grade 3
Hyponatremia
30
21
2
Grade 4
Sensory,
Gd
Grade 3, 3%
Hypocalcemia
47
7
3%
Alkaline phosphatase
37
2 2
Sensory,
Grade 1-2, 68%
Hypokalemia
21
7
2
Hyperkalemia
21
5
2
Infection/Pneumonia
12
7
Hyperglycemia
5
0
10
2030
40
5060
7080
90
100
% Affected
Breakdown of
of Neuropathy
Neuropathy
Symptoms
Neuropathic pain,
Grade 3, 3%
Motor,
Grade 1-2, 9%
Neuropathic pain,
Grade 1-2, 17%
Sensory,
Grade 3, 3%
Sensory,
Grade 1-2, 68%
Single Agent
Agent Bortezomib in as Upfront
Treatment in Higher than Average Risk
Myel
ye oma
PFS
OS
1-year
50%
88%
2-year
28%
76%
Outcomes with
with Bortezomib
Bortezomib ±
Dexamethasone
Reg
n
CR, %
VGPR, %
PR, %
OR, %
PFS, %
OS, %
Current
Bortez
39
0
5
44
49
1 yr 49
1 yr 88
study
Anderson
ASCO
Bortez
60
10
0
28
38
NR
NR
2006
Jagannath
Bt
Bortez
Br J
28*/63
40*/88
+/-
32
3*/6
9*/19
NR
1 yr 87
Haem
dex
2005
Jagannath
Br J
Bortez+/-
32
6
19
63
88
NR
NR
Haem
dex
2005
Harousseau
Haemat
Bortez-
48
21
10
35
66
NR
NR
ologica
Dex
2006
Conclusions
· In hi
hi h
g er than average risk
ti
pa
t
en s,
upfront bortezomib yields response
rates comparable
comparable to those reported
reported for
for
unselected cohorts of newly diagnosed
myeloma patients.
· For patients responding to therapy,
maintenance therapy
therapy is feasible.
· Reinduction was unsuccessful in
patients failing maintenance.
MD vs MDB for
for AL Amyloidosis
An ECOG protocol designed in collaboration with the
Systemic Amyloidosis Research Consortium
A. Dispenzieri/ M. Gertz/ S. Kumar (Mayo)
D. Seldin/V. Sanchorawala, MD (Boston University School of Medicine)
R. Comenzo (MSKCC, now at Tufts)
R. Abanour/ M. Benson (Indiana University
(y School of Medicine)
G. Merlini (University Hospital at San Matteo)
Upfront Bortezomib in Patients with
Higher than Average Risk Myeloma
· Ih
In i
hi h
g
i
r sk
t
pa i
ti
t
en s, upf
t
ron b t
or ezomib
ib
yields response rates comparable to
those reported
reported for
for unselected cohorts
cohorts of
newly diagnosed myeloma patients.
· For patients responding
responding to therapy,
maintenance therapy is feasible.
· Reinduction was unsuccessful in
patients failing maintenance.