Allogeneic Donor Transplants for
Multi
lti l
p e M
l
ye oma in S
ttl
ea e
· Number of Patients 278
· Transplant Dates 1977-2008
· Donors:
­ R l
e t
a d
e 213, U
l
nre t
a ed 65
· Regimens:
­ Ablative TBI + CY =30, + other =2
­ Ablative TBI (liver, lung shielding) +Bu (Cy) =47
­ Bu + Cy =58
Bu + Mel =7
­ Intermediate Mel (100) + Flu + TBI200cGy =14
­ Non Ablative TBI200cGy =62 + Flu =58

---

Donor Transplants for MM
Patient Characteristics
Ablative
nonAblative
Intermed
N=144
N=120
N=14
Age
46 (20-59)
53 (25-69)
52 (36-59)
Type
IgA31,IgG80,lc24
IgA30,IgG70,lc15
IgA5, IgG5,lc2
Responsive
p
23%
48%
42%
Dz at Allo
No Regimens
2 (1-6)
2 (1-6)
3 (2-50)
No Cycles
7 (1-32)
6 (3-40)
6 (4-15)
Relapse Auto
3%
34%
64%
Tandem
2%
74%
0%

---

Definitions
· Complete Response: per IMWG
· Partial Response: per IMWG
· Less than
than PR = Non-
Non Responder
· Riskgroup: If Response to last salvage
or primary therapy
therapy before Tx
Tx <PR
<PR,
patients were considered refractory

---

Response after Transplant
Ablative
NonAblative Intermed
N=145
N=120
N=14
CR
33 (23%)
50 (42%)
1
PR
33 (23%)
44 (37%)
4
NR
12 (8%)
23 (19%)
8
NE
67
3
1

---

Donor Transplants for Multiple Myeloma
Mortality Censored for Relapse
1
0.8
y
Ablative
lit 06
0.6
bi
0.4
p<0.0001
robaP
0.2
Non-Ablative
0
0
5
10
15
20
25
Years after Transplant
2/09

---

Donor Transplants for Multiple Myeloma
Risk of Relapse or Progression
1
p<0 0001
.
0.8
ylit 06
NonAblative
0.6
bi
0.4
robaP
Ablative
0.2
0
0
5
10
15
20
25
Years after Transplant
2/09

---

Donor Transplants for Multiple Myeloma
Risk of Acute GVHD Grade>3
1
0.8
p=0.01
ylit 06
0.6
bi
Ablative
0.4
robaP
0.2
NonAblative
0
0
25
50
75
100
Days after Transplant
2/09

---

Donor Transplants for Multiple Myeloma
Risk of Acute GVHD Grade>2
1
0.8
Ablative
ylit 06
0.6
bi
NonAblative
0.4
robaP
0.2
0
0
25
50
75
100
Days after Transplant
2/09

---

Donor Transplants for Multiple Myeloma
Risk of Chronic GVHD
GVHD
1
0.8
y
NonAblative
lit 06
0.6
bi
p=0.009
0.4
roba
Ablative
P
0.2
0
0
5
10
15
20
25
Years after Transplant
2/09

---

Non-Ablative Donor Transplants for Multiple Myeloma
Risk of Relapse Based on Ch
i
ron c GVHD
GVHD
1
NC
No
GVHD
CGVHD
0.8
yliti 06
0.6
b
0.4
CGVHD
robaP
0.2
P<0.0001
0
05
10
15
Years after Transplant
2/09

---

Multivariate Analysis of Factors
Affecting Outcomes
Outcomes All
-
Pts
Pts
HR,
Riskgroup
Tandem
Prep
p
l
va ue
SR
Sens v. R f
e
t
rac
Abla v. NA
NA
Survival
2.4 (1.7-3.4),
0.4 (.26-.54),
ns
.001
.001
TRM
1.9 (1.2-3.0),
0.4 (.18-.9), .02 0.5 (.26-.91),
.002
.001
RELAPSE
2.5 (1.8-3.3),
0.5 (0.4-.7),
ns
.0001
.0001
PFS
2.5 (1.8-3.3),
0.5 (0.4-.7),
ns
.0001
.0001
Other Variables examined: Age, Donor type, Number of
Pi
Prior
i
reg mens,
l
cyc es, XRT
XR C
, MV
CMV

---

Multivariate Analysis of Factors
Affecting Outcomes
Outcomes NonAblative
-
HR,
Riskgroup
Cyto/FISH
AutoRelapse
B2M
p value
Survival
2.2 (1.2-3.9),
2.4 (1.3-4.4), 2.5 (1.4-4.6),
.02
.01
.0001
RELAPSE
2.0 (1.3-3.2),
3.4 (2.1-5.6),
2.5 (1.2-5.3)
.0018
.0001
.01
PFS
20
2.0 (1
(1.3-
3 32
3. )
2),
34
3.4 (2
(2.1-
1 53
5. )
3),
25
2.5 (1
(1.2-
2 53
5. )
3),
.0018
<.0001
.01
Tandem Auto
Regimens
Tot
To al
a
TRM
0.3 (0.2-0.8),
1.5 (1.1-2.0),
.0027
.015
Other Variables examined: Age, Donor type, Number of
Prior cycles, XRT

---

Multivariate Analysis of Factors
Affecting Outcomes
Outcomes
HR (95%CI),
Riskgroup
Tx Number
Prep
Donor
p value
1 v. >1
Abla v. NA
Rel v. MUD
AGVHD>2
1.6 (1.2-2.3),
0.7 (0.5-0.9),
2.0 (1.4-2.8),
.0006
.008
.0005
CGVHD
1.9 (1.3-2.7),
0.001
Other Va
Variables
riables examined:
examined: Age,
Age, Relapse after
after autograft,
Tandem Auto-Allo, Number of Prior regimens, cycles, XRT

---

Allo Donor Transplants for Multiple Myeloma
Si
Survival by Regimen Intensit
ity
1
0.8
ylit 06
0.6
bi
nonAblative
P<0.0001
0.4
robaP
0.2
Ablative
Intermediate n=14
0
0
5
10
15
20
25
Years after Transplant
2/09

---

Allo Donor Transplants for Multiple Myeloma
Pi
Progression-FS
Free Survival by Regimen Intensit
ity
1
0.8
ylit 06
0.6
bi
P<0.0001
0.4
robaP
nonAblative
0.2
Ablative
Intermediate n=14
0
0
5
10
15
20
25
Years after Transplant
2/09

---

Non-Ablative Allo Donor Transplants for Multiple Myeloma
Progression-Free Survival
1
0.8
ylit 06
0.6
bi
0.4
roba
Related
P
0.2
Unrelated
0
05
10
Years after Transplant
2/09

---

Ablative Donor Transplants for Multiple Myeloma
Si
Survival by Decade
1
0.8
ylit 06
0.6
bi
0.4
roba
<1990 N 2
= 1
P
21
0.2
>1990 N=11
N=1 7
1
0
0
5
10
15
20
25
Years after Transplant
2/09

---

Allo Donor Transplants for Multiple Myeloma
Si
Survival Landmark from D tf
ate of Di
Diagnosis
1
0.8
ylit 06
P< 0001
0.6
.
bi
0.4
roba
nonAblative
rP
0.2
Ablative
0
0
5
10
15
20
25
Years after Transplant
2/09

---

Non-Ablative Donor Transplants for Multiple Myeloma
Survival by Cytogenetics/FISH
1
Nl or
0.8
p<0.0001
Hyerdiploid
y
Cyto, FISH
lit 06
0.6
neg
bi
0.4
robaP
0.2
Cyto/FISH pos
0
02
46
8
10
Years after Transplant
2/09

---

Tandem Auto->Non-Ablative Donor Transplants
for Multiple Myeloma
1
Survival by Prior Autograft Failure
0.8
ylit 06
0.6
bi
No Relapse
Relapse
0.4
robaP
0.2
0
02
46
8
10
Years after Transplant
2/09

---

Tandem Auto->Non-Ablative Donor Transplants
for Multiple Myeloma
Progression Free Survival by Prior Autograft Failure
1
0.8
p=0.002
yliti 06
0.6
b
0.4
No Relapse
robaP
0.2
Relapse
0
02
46
8
10
Years after Transplant
2/09

---

Survival after Tandem Auto->Non-Ablative Donor
Transplants for Multiple Myeloma
No Prior Autograft Failure
1
0.8
ylit 06
0.6
bi
Related =64
Unrelated =16
0.4
robaP
0.2
0
02
46
8
10
Years after Transplant
2/09

---

PFS after Tandem Auto->Non-Ablative Unrelated Donor
Transplants for Multiple Myeloma
No Prior Autograft Failure
1
0.8
ylit 06
0.6
bi
Related =64
0.4
robaP
Unrelated =16
0.2
0
02
46
8
10
Years after Transplant
2/09

---

Ablative Donor Transplants for Multiple Myeloma
PFS by Risk Group
1
0.8
ylit 06
P<0 0001
0.6
.
bi
0.4
roba
Responsive Disease
P
0.2
Resistant Disease
0
0
5
10
15
20
25
Years after Transplant
2/09

---

Non-Ablative Donor Transplants for Multiple Myeloma
PFS
PFS byR
by
iskG
Risk
roup
Group
1
0.8
P<0.0001
ylit 06
0.6
bi
Responsive Disease
0.4
robaP
0.2
Resistant Disease
0
0
5
10
15
Years after Transplant
2/09

---

---

Donor Stem Cell Transplants for
MM
· Non-ablative allografts have reduced TRM
hd
when compared
i
w th
ith abl
blati
tive regimens
· Grade 2 acute GVHD is lower with NA
allografting but with more CGVHD
· Relapse after NA allografting is higher
· Tandem auto-NA allo and chemoresponse prior
to tandem are associated with better PFS, OS
and lower relapse
· Cytogenetics/FISH impact OS
OS after
after NA
NA allo,
allo,
· ß-2m impacts PFS, Relapse

---

Donor Stem Cell Transplants for
MM
· Relapse after tandem
tandem autologous->NA
allografting remains a major cause of treatment
failure
· Melphalan 100 mg/m2 in a very small series did
not improve outcomes
· Solutions:
­ Post allograft
allograft maintenance
maintenance-lenalinomide
-
, bortezomib
­ More targeted therapies-> radioisotope ablation,
adding novel therapies to NA reg
gpgimen

---

Acknowlegdements:
· Fred Hutchinson Cancer Center
­ Dave Maloney
­ Marcello Rota
­ Rainer Storb
­ Fred Appelbaum
­ Gary Shock
· Seattle Veterans Hospital
­ Tom Chauncey
Chauncey

---