Table 3.
Randomized trials comparing tandem autologous stem cell transplantation with autologous followed by allogeneic stem cell transplantation in patients with multiple myeloma.
| Reference | N | Regimen | TRM | Response | PFS* | OS* | Comments |
|---|---|---|---|---|---|---|---|
| Garban et al.(75) | 284 | Initial ASCT MEL 200 Tandem ASCT MEL 200+Dex Or MEL 220+Dex+B- E8 Allo-SCT Bu-Flu-ATG |
Tandem ASCT 5% Allo-SCT 10.9% |
CR/VGPR Tandem ASCT 51% Allo-SCT 62.2% |
EFS Tandem ASCT 30 months Allo-SCT 25 months P=0.56 |
Tandem ASCT 41 months Allo-SCT 35 months P=0.27 |
|
| Rosinol et al.(76) | 110 | Initial ASCT VBMCP/VBAD Tandem ASCT MEL 200 or CVB Allo-SCT Flu+Mel |
Tandem ASCT 5% Allo-SCT 16% P=0.09 |
CR Tandem ASCT 11% Allo-SCT 40% P=0.001 |
Tandem ASCT 31 months Allo-SCT Not-reached P=0.08 |
Tandem ASCT 58 months Allo-SCT Not-reached P=0.9 |
Plateau in PFS seen in allo-SCT group |
| Bruno et al.(77) | 162 | Initial ASCT MEL 200 Tandem ASCT MEL 100 – 200 Allo-SCT TBI (200 cGy) |
Tandem ASCT 2% at 2-year Allo-SCT 10% at 2-year P=0.09 |
CR Tandem ASCT 26% Allo-SCT 55% P=0.004 |
EFS Tandem ASCT 29 months Allo-SCT 35 months P=0.02 |
Tandem ASCT 54 months Allo-SCT 80 months P=0.01 |
On multivariate analysis allo-SCT was associated with longer EFS and OS |
| Björkstrand et al.(80) | 357 | Initial ASCT MEL 200 Tandem ASCT MEL 200 Allo-SCT Flu-TBI (2 Gy) |
Tandem ASCT 4% at 5- year Allo-SCT 16% at 5-year P=<.001 |
CR Tandem ASCT 41% Allo-SCT 51% P=0.020 |
At 60-months Tandem ASCT 18% Allo-SCT 35% P=0.001 |
At 60-months Tandem ASCT 58% Allo-SCT 65% P=0.006 |
On intention- to-treat analysis of high-risk patients, allo-SCT was associated with longer PFS and OS |
| Krishnan et al.(84) | 710 | Initial ASCT MEL 200 Tandem ASCT MEL 200 (patients were then randomized to maintenance therapy with thalidomide+Dex or observation) Allo-SCT TBI (2 Gy) |
Tandem ASCT 4% at 3- year Allo-SCT 11% at 3-year P=<.0001 |
CR Tandem ASCT 45% Allo-SCT 58% P=0.007 |
At 3-year Tandem ASCT 46% Allo-SCT 43% P=0.67 |
At 3-year Tandem ASCT 80% Allo-SCT 77% P=0.191 |
|
| Lokhorst et al.(85) | 260 | Initial ASCT MEL 200 (followed by maintenance therapy with IFN or thalidomide. 3 patients received tandem ASCT) Allo-SCT TBI (2 Gy) |
No donor 3% Donor available 16% P=<0.001 |
CR No donor 37% Donor available 43% P=0.67 |
At 6-year No donor 22% Donor available 28% P=0.17 |
At 6-year No donor 55% Donor available 55% P=0.72 |
Cumulative incidence of relapse at 6-year was significantly lower in patients with a donor versus no donor group (55% vs. 77%; P=0.005) |
| Knop et al.(86) | 199 | Initial ASCT MEL 200 Tandem ASCT MEL 200 Allo-SCT Flu+Mel+ATG (for unrelated donors) |
- | CR Tandem ASCT 32% Allo-SCT 59% =0.003 |
At 3-yr Tandem ASCT 72% Allo-SCT 60% P=0.22 |
Legend:
Bu, busulfan; Flu, fludarabine; ATG, anti-thymocyte globulin; Dex, dexamethasone; B-E8, Anti-IL6 antibody; VBMCP: vincristine, BCNU, melphalan, cyclophosphamide, prednisone VBAD: vincristine, BCNU, adriamycin, dexamethasone; CVB: cyclophosphamide, etoposide, BCNU; MEL, melphalan; TBI, total-body irradiation; IFN, interferon
ASCT, autologous stem cell transplantation; allo-SCT, allogeneic stem cell transplantation; TRM, treatment-related mortality; EFS, event-free survival; CR, complete remission; VGPR, very good partial remission; PFS, progression-free survival; OS, overall survival; * CR rate for tandem ASCT: CVB 3%, Mel 35%, P=<0.001
Median PFS and OS, unless specified otherwise.