Myeloma
Outcome Following Early Relapse after
Autologous Stem Cell Transplantation
for Multiple Myeloma
Syed T. Mahmood, Shaji Kumar, Martha Q. Lacy, Angela
Di
i
spenz eri, Suzanne R. Hayman, S. Vincent R j
a k
jkumar, M
k
ar
R. Litzow, Morie A. Gertz
Mayo Clinic, Rochester, MN
Background
Autologous stem cell transplant (ASCT) improves
survival in myeloma
Patients invariably relapse after ASCT
V i
ar ous i
r sk factors have been identified for post ASCT
relapse
Outcome of patient relapsing early after ASCT is not
known
Objective of Study
To t
s d
u y the
t
ou come f
o
ti
pa
t
en s h
w o l
re apse / progress
early (<12 months) after upfront autologous stem cell
transplant (ASCT) for Multiple Myeloma
Materials and Methods
432 patients with newly diagnosed Multiple Myeloma
transplanted between 1994 and 2005
All patients underwent ASCT within 12 mos of diagnosis
Pati
tients were di id
v ed i t
n o 2 groups:
1. Early relapse (relapse/progression <12 mos from ASCT)
2. Late relapse (either relapsed/ progressed >12 months after ASCT
or have not at last follow up)
Baseline features: Initial Therapy
Single agent Dexamethasone: n=166 (38.5%)
Vincristi
tine, doxorubi
bicin, and dexameth
thasone (VAD): n
= 129 (29.9%)
Thalidomide-Dexamethasone: n = 117 (24.8%)
8%)
The remaining patients received :
Revlimid/Dex
Revlimid/De amethasone
x
(n=16)
Vincristine/BCNU/melphalan/cyclophosphamide/ prednisone
(VBMCP) (n=5)
Other regimens (n=8)
Baseline features: Stem Cell Collection
Stem Cells were collected using granulocyte colony-
stimulating factor (G-CSF) alone in 172 (39 7
. %)
7%) of
patients
260 (60.3%) of patients had stem cells collected after
receiving cyclophosphamide for 2 days then GM-CSF or
G-CSF starting on day 3
Baseline features: Conditioning
81.3% of patients underwent conditioning with
melphalan alone at 200mg/m2
melphalan alone at 200mg/m
8.5%
5% of patient received dose reduced melphalan at 100-
140 mg/m2 for advanced age, renal insufficiency or poor
performance.
10.2% of patients received melphalan 140mg/m2
10.2% of patients received melphalan 140mg/m
followed by total body radiation (12 Gy) (all prior to June
2000)
Results: Baseline Features at Transplant
Early Relapse
Late Relapse
Characteristics
P-value
(N=94)
(N= 338)
Variable
Median (range)
Median (range)
Age at diag
ggnosis
56.2 (35
5(35.5-72.2)
7)
57.5 (29.4-75.4)
NS
Age at Transplant
56.6 (36.1-72.9)
58.7 (30-75.8)
NS
Time to Transplant
6.3 (1-11.5)
6.0 (2-11.9)
NS
Serum M P t
ro i
e n level
1.3 (0-6)
6.9)
0.9 (0-6)
6.9)
NS
BM Plasma Cell %
14 (0-95)
8.4 (0-91)
NS
LDH
179.5
182
NS
Creatinine
1 (0.6-8.6)
1 (0.6-10.1)
NS
Results: Baseline Features at Transplant
Early Relapse Late Relapse
Characteristics
P-value
(N=94)
(N= 338)
Variable
%
%
Gender: male
61.7
57.7
NS
PCLI >/= 1%
41.9
15.5
< 0.001
2 Microglobulin >3.5 mg/dL
28.7
23.1
NS
Bone disease
12.8
15.4
NS
Rf
Ref
t
rac ory at t
l
ransp
t
an
41.5
29.3
00
0. 3
03
Durie Salmon:
Stage: 2
27.6
36.2
NS
Stage: 3
72.4
63.8
NS
> 1 Induction regimen
18
8
0.007
Abnormal Karyotype
34
14.8
< 0.0001
Circulating PC at Collection
51 1
.
36 4
.
00
0. 1
01
Results: Response rates
El
Early Relapse
Lt
Late Relapse
(N=94)
(N= 338)
Overall Response
96%
96%
Complete Response
18%
43%
Post-ASCT overall survival
1. 0
0. 8
Lat e R e l a ps e
E a r l y R e l aps e
l
0. 6
a
n=338, median 75.7 mos
ivrv
Su
0. 4
0. 2
n=94, median 17.6 mos
P < 0.001
0. 0
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
140
160
Ti m e
Overall survival from diagnosis
1. 0
0. 8
Lat e R e l aps e
Ea r l y R e l a p s e
0. 6
al
n=338, median 82.2 mos
ivv
Sur
04
0 . 4
0. 2
n=94, median 23.9 mos
P < 0.001
0. 0
0
2 0
4 0
6 0
8 0
1 0 0
12 0
1 4 0
16 0
1 80
Ti m e
Overall survival from relapse
1. 0
0. 8
L a te R e l a p s e
Ea r l y R e l a p s e
0. 6
alivv
Sur
0. 4
n=169, median 39.6 mos
0. 2
n=94, median 7.8 mos
P < 0.001
0. 0
0
2 04 06 08 0
1 0 0
Ti m e
Results: Risk Factors for Relapse < 12 mos (univariate)
Variable
HR (95% CI)
P-Value
>1 Induction Regimen
2.5 (1.3, 4.9)
0.005
Refractory @ Tx
1.7 (1.1, 2.8)
0.03
BMPC > 30%
2.4 (1.4-4.1)
0.002
PCLI > 1%
39
3.9 (2
(2.4, 65
6. )
5)
< 0 0001
.
Abnormal karyotype
3.0 (1.8, 5.1)
< 0.0001
No CR
3.1 (1.7, 5.4)
0.002
Circulating PC at harvest
1.8 (1.2, 2.9)
0.01
Results: Risk Factors for Relapse<12 m (multivariate)
Variable
HR (95% CI)
P-Value
>1 Induction Regimen
2.3 (1.1, 5.0)
0.03
PCLI >= 1%
2.9 (1.6, 5.4)
0.0005
No CR
CR
3.2 (1.8, 5.9)
0.0002
Results: Prognostic Factors for OS from ASCT
Variable
HR (95% CI)
P-Value
PCLI > 1%
15
1.5 (1
(1 0
. 2
02, 21
2. 8)
18)
00
0. 37
037
2M > 5.5 mg/dL
2.2 (1.3, 3.5)
0.002
Relapse < 12 mos from
7.3 (5.1, 10.6 )
< 0.0001
ASCT
Results: Effect of time of relapse
1. 0
0. 8
Ea r l y
Before 2002
La t e
From 2002
l
0. 6
aivrv
Su
P=0.04
0. 4
n=67, median 20.5 mos
0. 2
n=27, median 12.5 mos
0. 0
0
2 04 0
6 08 0
1 0 0
Ti me
Conclusions
Early relapse after ASCT represents a novel predictor for
poor outcome
These patients have hig
pgh risk disease that may not be
obvious from conventional risk factors
These patients should be enrolled in clinical trials
examining novel drugs and combinations
These numbers provide a reference baseline for these
trials