Role of Autologous Stem Cell Transplant after Induction Therapy with Bortezomib-Thalidomide or
Bortezomib-Lenolidomide in Newly Diagnosed Multiple Myeloma Patients
Nina Shah, Donna Weber, Robert Orlowski, Michael Wang, Sheeba Thomas, Tiffany Richards, Sergio Giralt, Muzaffar Qazilbash, Raymond Alexanian, Jatin Shah
University of Texas M.D. Anderson Cancer Center
INTRODUCTION
FIGURE 1: RESPONSES
FIGURE 2: RESPONSE RATES IN PATIENTS TREATED WITH UP-FRONT BTD OR
BLD AND SUBSEQUENT HIGH DOSE CHEMOTHERAPY PLUS ASCT
Multiple myeloma is the second most common hematologic malignancy and to
date, is considered incurable.
Induction BTD or BLD
100-Day Post aSCT
1%
0%
Bortezomib-Thalidomide-Dexamethasone
Bortezomib-Lenolidomie-Dexamethasone
8%
Novel therapeutic options such as bortezomib and immunomodulatory agents
2%
0%
25%
60
50
(IMiDs: thalidomide or lenolidomide) have significantly improved complete
CR
45
50
response (CR) rates in up-front management of multiple myeloma.
37%
40
,%
VGPR
,%
te 40
Induction Response
35
a
te
42%
a
Induction Response
R
30
PR
e 30
R
s
100-Day Post-Transplant
25
Preclinical data suggests that IMiDs potentiate the activity of bortezomib. This
se
SD
n
20
Response
20
100-Day Post-Transplant
pon
o
47%
s
Response
has been substantiated clinically by improved induction response rates of
e
15
Prog Disease
R 10
espR 10
combination bortezomib-thalidomide-dexamethasone (BTD) and bortezomib-
0
5
lenolidomide-dexamethasone (BLD) over TD and LD.
38%
CR
VGPR
PR
SD
Progressive
0
Disease
CR
VGPR
PR
Consolidation with high dose chemotherapy and autologous stem cell
transplant (aSCT) improves survival in eligible multiple myeloma patients.
However, the role of aSCT after induction with new highly active agents is
Table 1: PATIENT CHARACTERISTICS
unclear
CHARACTERISTICS
BTD
BLD
Figure 3: EVOLUTION OF CLINICAL RESPONSES FROM INDUCTION
Number of Patients
77
19
CHEMOTHERAPY TO 100 DAYS POST-TRANSPLANT
In patients newly diagnosed with multiple myeloma treated with BTD or
BLD followed by high dose chemotherapy and aSCT, we studied the
Male
53 (69%)
11 (58%)
40
evolution of clinical responses from induction chemotherapy to 100 days
Female
24 (31%)
8 (42%)
9
35
ts
post-transplant
8
ts
Median Age (Years)
56
57
30
ien
7
ien
25
6
International Staging System Stage:
fPat 20
o
Induction
fPat 5
o
I
29 (38%)
9 (47%)
erb 15
4
er
m
chemotherapy
b 3
II
26 (34%)
4 (21%)
u 10
m
N
u 2
5
N
III
19 (25%)
6 (32%)
1
METHODS
0
0
CR
VGPR
PR
Stable
Progression
Myeloma Subtypes
CR
VGPR
PR
Single-center, retrospective chart review of 96 multiple myeloma patients
IgG
29 (38%)
7 (37%)
treated from 2003 to 2008 with an induction regimen of either BTD or BLD and
IgG
14 (18%)
2 (11%)
Bortezomib-Thalidomide-Dexamethasone
Bortezomib-Lenolidomide-Dexamethasone
consolidated with high dose chemotherapy and aSCT.
IgA
12 (16%)
4 (21%)
IgA
8 (10%)
1 (5%)
Progression
Response to induction therapy (pre-transplant) and 100 day post-transplant
IgD
2 (3%)
1 (5%)
40
PR
Stable
9
35
VGPR
response were graded according to International Myeloma Working Group
IgD
1 (1%)
0 (0%)
PR
ts 8
ts 30
CR
VGPR
ien 7
criteria
IgE
1 (1%)
0 (0%)
ien 25
CR
100 Days
6
IgE
0 (0%)
0 (0%)
20
fPat 5
fPat
o
o
Post-Transplant
Light Chain
7 (9%)
3 (16%)
15
er 4
er
b
b 10
3
m
Light Chain
3 (4%)
1 (5%)
m
u
u
5
2
N
RESULTS
N
1
Response to Induction Therapy
0
Induction CR
Induction
Induction
Induction
Induction
0
CR
6 (8%)
2 (11%)
VGPR
PR
Stable
Progression
Induction CR
Induction VGPR
Induction PR
Of the 96 patients who underwent induction with BTD or BLD, CR, VGPR and PR
VGPR
37 (48%)
8 (42%)
were achieved in 8 (8%), 45 (47%) and 40(42%) respectively for an ORR of 93/96
PR
31 (40%)
9 (47%)
(97%) (Figure 1).
SD
2 (3%)
0 (0%)
Progressive Disease
1 (1%)
0 (0%)
After aSCT CR, VGPR and PR were achieved in 36 (38%), 36 (38%) and 24
Overall Response To Induction Therapy
74 (96%)
19 (100%)
(25%) respectively for an ORR of 96/96 (100%) (Figure 1).
CONCLUSIONS
Response at 100 Days Post-aSCT
CR
27 (35%)
9 (47%)
Up-front use of novel therapeutic agents has improved response rates in multiple myeloma
Notably, 20/45 (44%) of patients with a VGPR after induction therapy with BTD or
VGPR
31 (40%)
5 (26%)
BLD improved to a CR after aSCT. 8/41 (20%) of patients with an initial PR to
Autologous stem cell transplant further improves response rates in patients demonstrating relative
PR
19 (25%)
5 (26%)
BTD or BLD improved to a CR and 10/41 (24%) with a PR improved to VGPR
SD
0 (0%)
0 (0%)
resistance to induction chemotherapy with bortezomib-thalidomide-dexamethasone or bortezomib-
after aSCT.
Progressive Disease
0 (0%)
0 (0%)
lenolidomide-dexamethasone.
Overall Response at 100 Days Post-aSCT
77 (100%) 19 (100%)