Tandem AutHCT with or without Maintenance
Therapy (auto-auto) versus Single AuHCT Followed
by HLA Matched Sibling Non-Myeloablative
Allogeneic HCT (auto-allo) for Patients with
Standard Risk Multiple Myeloma: Results from the
BMT-CTN 0102 Trial
Amrita Krishnan, Marcelo Pasquini, Marian Ewell, Edward A. Stadtmauer,
Edwin Alyea III, Joseph Antin, Raymond Comenzo, Stacey Goodman,
Parameswaran Hari, Robert Negrin, Muzaffar Qazilbash, Scott Rowley,
Firoozeh Sahebi, George Somlo, David Vesole, Dan Vogl, Daniel Weisdorf,
Nancy Geller, Mary M. Horowitz, Sergio Giralt, David Maloney
On behalf of the Blood and Marrow Transplant Clinical Trials Network
Introduction
AuHCT improves survival in patients with MM, but disease
relapse and progression remain a challenge.
Both tandem AuHCT and post transplant maintenance
therapy improve PFS.
Allogeneic HCT has the potential to reduce disease
progression further through a graft-versus-myeloma effect
but is associated with significant TRM.
Non-myeloablative conditioning regimens allows the
allogeneic approach to be used with reduced TRM.
BMT CTN 0102 Study Schema
Multiple Myeloma
meeting
eligibility criteria
HLA typing of all patients
*Biologic assignment
with siblings
occurred when HLA-typing
High-dose melphalan (200 mg/m2)
results were available. The
+ autologous PBSC transplant
time range from prior to first
transplant to at most 30 days
Biologic assignment*
after first transplant.
Eligible HLA-matched
No eligible HLA-matched
sibling donor
sibling donor
60 to 120 days
Non-myeloablative conditioning
High-dose melphalan (200 mg/m2)
TBI 200 cGY
+ autologous PBSC transplant
allogeneic PBSC transplant
Randomization
Randomization occurred
Thalidomide
Observation
Dexamethasone
once patients were assigned
x12 months.
to auto-auto
PRIMARY ENDPOINT : 3yr Progression Free Survival
Survival Outcomes after the First Transplant:
Auto-Auto vs. Auto-Allo
Progression-free Survival
Overall Survival
100
100
Auto/Auto, 80% @ 3yr (95% CI, 77-84%)
90
90
80
Auto/Auto, 46% @ 3yr (95% CI, 42-51%)
80
70
70
,% 60
60
Auto/Allo, 77% @ 3yr (95% CI, 72-84%)
50
50
Probability 40
40
Auto/Allo, 43% @ 3yr (95% CI, 36-51%)
30
30
20
20
10
10
P-value = 0.67
P-value = 0.19
0
0
Months 0
6
12
18
24
30
36
42 48 0
6
12
18
24
30
36
42
48
# at risk:
Auto/Auto 436
395
348
292
242
213
178
54
42 436
424
406
395
370
348
305
107
79
Auto/Allo 189
165
138
117
105
89
71
23
16 189
183
167
160
156
143
124
43
27
Mp10_5.ppt
Cumulative Incidence of Disease Progression/Relapse
and Treatment-Related Mortality after First Transplant
Progression/Relapse
Treatment-related Mortality
100
100
P-value = 0.41
P-value < 0.001
90
90
80
80
% 70
70
60
60
Auto/Auto, 46% @ 3yr (95% CI, 41-50%)
Incidence, 50
50
40
40
Cumulative 30
30
20
Auto/Allo, 40% @ 3yr (95% CI, 33-47%)
Auto/Auto, 4% @ 3yr (95% CI, 2-5%)
20
10
Auto/Allo, 12% @ 3yr (95% CI, 7-16%)
10
0
0
012
618
24
30
36
42
48 012
618
24
30
36
42
48
Months
Months
Mp10_7.ppt
Conclusions
There were no differences in 3-year PFS and OS
between patients receiving auto-auto or auto-allo
transplant.
Potential benefits of graft-versus-myeloma to reduce
disease progression or relapse were offset by
increased TRM.
Thal-Dex maintenance did not improve PFS or OS,
likely due to poor tolerability or compliance with this
regimen.