A Phase II Trial of Myeloma Induction Therapy With
Cyclophosphamide, Bortezomib and Dexamethasone (Cybor-D):
Improved Response Over Historical Lenalidomide-
Dexamethasone Controls
Craig B. Reeder, M.D.1, Donna E. Reece, M.D.3, Rafael Fonseca, M.D.1,
P. Leif Bergsagel, M.D.1, Joseph Hentz, MSc.1*, Nicholas A. Pirooz,
BSc.1*, Jacy E. Boesiger, RN.1*, Jesus G. Pisa, M.D.3*, Vishal Kukreti,
M.D.3, Christine Chen, M.D.3, Suzanne Trudel, M.D.3, Joseph R. Mikhael,
M.D.3, Martha Lacy, M.D.2, S. Vincent Rajkumar, M.D.2 and A. Keith
Stewart, M.D.1.
1Hematology/Oncology, Mayo Clinic, Scottsdale, AZ, United States,
85259-5494; 2Hematology/Oncology, Mayo Clinic, Rochester, MN, United
States, 55905 and 3Hematology/Oncology, Princess Margaret Hospital,
Toronto, Ontario, Canada, M5G 2C1.
Disclosure Statement
Employment: no
Consultancy: yes, Fonseca, Stewart, Reece
Ownership: no
Ownership Interest: no
Research funding: yes, Reeder, Stewart for this trial
Honoraria: no
Financial relationship: no
Off label use: yes, Bortezomib in newly diagnosed MM
Background
Cyclophosphamide (Cy), Bortezomib (BZ) and Dexamethasone
(Dex) all have single agent activity in Multiple Myeloma (MM)
Stewart etal. previously reported an 85% response rate with
54% CR in relapsed MM using a combination of Cy, BZ and
prednisone
Rationale: Cy, BZ and Dex should have significant activity in
newly diagnosed patients with MM
Study Goal
Response rates: CR, nCR, VGPR
Overall response
Progression free and overall survival
Toxicity of the CyBor-D regimen
Schema
Newly Diagnosed Myeloma
Cyclophosphamide 300 mg/m2 p.o. weekly, days 1, 8, 15, 22
Bortezomib 1.3mg/m2 i.v. days 1, 4, 8, 11
Dexamethasone 40mg p.o. days 1 4, 9 12, 17 2 0
(Q28 day cycles)
4 cycles (16 weeks)
Response Assessment
*Stem cell Collection
Off Study To Transplant
OR
Continue Meds for further
8 cycles
Methods
33 patients enrolled to date
23 evaluable for response and toxicity after at least one cycle of
CyBor-D
14/30 have completed 4 cycles
Response defined according to IMWG criteria though bone
marrows are not yet available for all patients to confirm CR
Responses are compared to a control group who received what
many consider a standard induction regimen of Lenalidomide and
Dexamethasone (L-Dex) (Rajkumar, Blood, 2005;106:4050-3)
Updated Response - % decline in M-protein
Cycle 1
Cycle 2
Cycle 3
Cycle 4
CyBor-D
66
83
85
93
L-Dex
67
78
81
80
CYBOR-D SPEED AND DEPTH OF RESPONSE IS SUPERIOR TO
Rev-Dex
Mean % M PROTEIN DECLINE WITH TIME
120
100
80
TNE
CYBORD (n=23)
C
60
RD (n=33)
PER
40
20
0
NE
E 1
E 2
E 3
E 4
CL
CL
CL
CL
SELI
BA
CY
CY
CY
CY
CYCLE NUMBER
Updated Response - % in VGPR after each cycle
Cycle 1
Cycle 2
Cycle 3
Cycle 4
CyBor-D
26
55
68
86
L-Dex
18
36
42
33
VGPR or Better by Cycle
1
P=0.003
0.9
0.8
0.7
RP 0.6
GV
CYBORD
t> 0.5
RD
rcen 0.4
Pe 0.3
0.2
0.1
0
CYCLE 1
CYCLE 2
CYCLE 3
CYCLE 4
Cycle Number
Response after Cycle 4
CYBOR D
LEN-DEX
CR
1/14 ( 7%)
5/30 (17%)
NCR
8/14 (57%)
1/30 ( 3%)
VGPR
3/14 (21%)
4/30 (13%)
PR
2/14 (14%)
16/30 (53%)
MR
0/14 ( 0%)
1/30 ( 3%)
SD/NR
0/14 ( 0%)
3/30 (10%)
At least nCR in 64% of patients
Results Toxicity
Gr 3 hematologic 24%, neutropenia 20%
Gr 3 hyperglycemia 17%
Gr 3 sensory neuropathy 5%
Overall incidence of neuropathy 69%
Gr 3 Infection 5%
Conclusions
CyBor-D induction therapy is highly active in newly diagnosed
MM
64% in CR or nCR and 86% in VGPR or better after 4 cycles
CyBor-D produces more profound responses than the best
standard therapy, Lenalidomide and dexamethasone
CyBor-D has manageable toxicities