Single Agent Bortezomib is associated with
a High Response Rate in Patients with High
Risk Myeloma.
A Phase II Study from the Eastern Cooperative
Oncology Group (E2A02) . Abst. 3527
A Dispenzieri, MD1, L Zhang, MS2, D Vesole, MD3, R Fonseca, MD4, and PR Greipp, MD1.
1Mayo Clinic Rochester, MN; 2Eastern Cooperative Oncology Group, Boston, MA; 3St.
Vincents Comprehensive Cancer Center, New York, NY; 4Mayo Clinic, Scottsdale, AZ.
AIMS
1. Evaluate response rate of bortezomib
in high-risk myeloma
2. Assess progression free survival
3. Assess maintenance schedule of
bortezomib
ELIGIBILITY
· Previously untreated active myeloma
· Adequate performance status and organ
reserve
· High Risk Myeloma, any of the
following:
· ISS 3 (2M 5.5)
· PCLI 1
· Del 13q
E2A02: Schema
Low Platelets
Anemia
Neutropenia
Abn. Electrolytes
Adverse
Fatigue
Neuropathy
Nausea
Events
Abn. LFT
Hyponatremia
Colits/diarrhea
Grade 1,2
Pain
Grade 3
Rash
Infections
Grade 4
GI pain
Grade 5
Dyspnea/
hypoxia
Edema
Ocular
Psychiatric
Syncope
Cardiac dysfunction
Pancreatitis
Arrhythmias
020
40
60
80
100
% of Patients
RESPONSE RATES ITT (3
unevaluable) MinimalResponse
Partial Response
Very Good Partial
Response
60
52
47
54
50
50
50
50
7
9
17
40
25
40
30
esponding
40
41
39
R% 20
33
25
10
10
5
6
6
0
All
PCLI
ISS 2M
M- 13
F- 13
t(4;14)
1
5.5
Responders 22/42
8/17
18/33
3/6
5/10
2/4
# Affected
Response rates, ITT (n=42; 11
`uneval')*
60
47
45
Minimal Response
43
50
Partial Response
Very Good Partial
6
5
Response
40
30
25
30
esponding
41
R
17
%
36
36
20
30
25
10
17
6
2
3
0
All
PCLI
ISS 2M
M- 13
F- 13
t(4;14)
1
5.5
Responders
18/42
8/17
15/33
1/6
3/10
1/4
# Affected
*Fig. 3: If missing 24 hour urine, pat
patient
ient deemed `unevaluable' even if clear serum response;
response; these patients
deemed `evaluable' in Fig 4.
OVERALL SURVIVAL
1.0
0.8
0.6
Probability
0.4
Survival 0.2
0.0
010
20
30
Time (months)
-
PROGRESSION FREE SURVIVAL
1.0
yitilb 0.8
ab 0.6
ProS 0.4
PF
0.2
Median 9.9 months
0.0 010
20
30
Time (months)
PFS OF PATIENTS ON
MAINTENANCE
1.0
15 PATIENTS
0.8
7 EVENTS
0.6
Survival
0.4
MEDIAN PFS, months...
From on-study = 20.5
Free
From maintenance = 14.7
0.2
Progression
0.0
010
20
30
CONCLUSIONS
· Response rates are high in high-risk, newly
diagnosed myeloma patients
· The regimen was well tolerated with the
most common AEs being
myelosuppression, fatigue, and
hyponatremia
· Grade 1-2 PN occurred in 60% of patients
while grade 3 occurred in only 5%.