Is there a place for allogeneic
transplantation in myeloma
myeloma in
in the
the
era of novel agents?
Jayesh Mehta MD
Professor of Medicine
Director, HSCT Program
Feinberg School of Medicine
Robert H Lurie Comprehensive Cancer Center
Northwestern University
Graft-versus-myeloma 1st case
Allografted in 1988 CR attained after T cell infusions
OS after allogeneic BMT
7-year EFS 22%
US Intergrroup 9321
CI Allograft
What does an allograft offer?
I
Graft-versus-myeloma
I
High response rates
Autograft
I
Prolongation of survival
I
Cure
CI Allograft
g
What else does an allograft offer?
I
Graft-versus-myeloma
N GVHD
I
High response rates
CI Allograft
N High complication rates
I
Prolongation of survival
N Compromised quality of
of life
Autograft
I
Cure
N Transplant related
-
morta
morta
ality
OS after allogeneic BMT
7-year EFS 22%
US Intergrroup 9321
CI Allograft
Ideal approach to allogeneic HSCT in myeloma
I
Biologic nature of the disease
N Expected outcomes with
with differ
differrent approaches
I
Patient factors
10
10
N Age
g
9
Autograft
9
N Comorbidities
8
8
Allograft
N PS
7
7
I
Donor avail
il b
a ilit
bility
6
6 Sa
f
5
ggressive disease
5 et
fficacy
Ag
y
E 4
4
3
3
Advanced age
2
Poor performance status 2
1
Organ dysfunction
dysfunction 1
0
0
Why are allografts thought to be awful?
I
Because they are more misused than used...
N The Mallory approach
N The Mortuus Equus approach
"Because it's there"
I
George Mallory, 1924
N Upon being asked why he
he
wanted to climb Mount
Everest
The Mallory Approach
I
Have donor?
N Will allograft!
I
Consequences
q
N Patients likely to do well with
other approaches end up
being allografted
allografted
· Iatrogenic adverse outcomes
come into sharp focus
TRM
GVHD
Compromised QOL
An example of the Mallory Approach
The Last Resort
The Mortuus Equus Approach
I
Allografting when all other options have been
exhausted
N Poor performance status
N Compromised organ function
N Refractory, multiply relapsed disease
I
Consequences
N Patients who may be candidates for palliative care
end up
up being
being allografted
· Disease-related adverse outcomes come into sharp
focus
Universal relapse
Short duration of disease control
So what's one to do?
I
Judicious use of allogeneic
I
Studies aimed at improving
HSCT
outcomes
N High risk of TRM
N Tandem auto-allo
· Avoid allograft
N Better conditioning
· Alternati
tive approaches
regimens
N High risk of disease
· Intensity matters
progression
N Better GVHD prophylaxis
· Consider allograft early
· Graft manipulation
Dissociation of GVHD
and GVM
N Good supportive care
N Post-transplant therapy
· Ih
Immunotherapy
· Anti-myeloma therapy
"Plateau uncommon after an RIC allograft"
EBMT RIC
PETHEMA
Auto-allo vs tandem auto
It's the same with the new agents!
Lenalidomide
Thalidomide
Bortezomib
Novel agents after allogeneic HSCT...
Treatment of relapse after allograft
Maintenance therapy with novel agents after an allograft
L
lid
ena
omide especiall
lly att
ttracti
tive because fi
of t
its i
d
mmunomo
l
u atory acti
tions
How should allografts be used?
I
High-risk disease Early transplantation
N Novel agents in combination for induction
induction
N Mel200 autograft
Clinical trials
N Tandem miniallograft
N Post-allograft maintenance
I
Non-high-risk disease Late transplantation
N Selected patients
N Chemosensitive disease
N Failure of a limited number of prior regimens
I
Other Usually late transplantation
N MDS
N Tt
Treat
t
men id
-induced marrow ffail
ailure
· Especially if autologous cells not available to restore BM function
Conclusion
I
Is there a place for
allogeneic HSCT in
myeloma today?
N Yes
I
Is there a place
place for
"allogeneic transplanters"
in myeloma?
N Definitely not!