Summary of high-dose therapy trials in multiple myeloma
Study . | Randomization . | Regimens . | N . | Mean age, y . | Median FU, mo . | % CR (P) . | EFS, median mo. (P) . | OS, median mo. (P) . |
|---|---|---|---|---|---|---|---|---|
| Standard-dose therapy vs high-dose therapy | ||||||||
| Attal et al8 IFM 90* | Before treatment | VMCP/BVAP × 18 vs VMCP/BVAP × 4-6 → CTX + MEL 140 + TBI 8 Gy | 100 vs 100 | 58 vs 57 | 108 | 14 vs 38 (< .001) | 18 vs 28 (.01) | 44 vs 57 (20% vs 35% @ 7 y) (.03) |
| Child et al16 MRC VII* | Before treatment | ABCM × 4-12 vs CVAMP × 3 → CTX + MEL 200 | 200 vs 201 | 56 vs 55 | 42 | 8 vs 44 (< .001) | 20 vs 32 (16% vs 36% @ 4 y) (< .001) | 42 vs 54 (46% vs 55% @ 4 y) (.04) |
| Blade et al50 PETHEMA† | Responders to induction | ABCM/VBAD × 12 vs ABCM/VBAD × 4 → MEL 200 | 83 vs 81 | 56 vs 56 | 66 | 11 vs 30 (< .002) | 34 vs 43 NA | 67 vs 65 NA |
| Single transplantation vs tandem transplantation | ||||||||
| Attal et al15 IFM 94* | Before treatment | VAD × 3-4 → G-CSF→ MEL 140 + TBI 8 Gy vs VAD × 3-4 → G-CSF→ MEL 140; MEL 140 + TBI 8 Gy | 199 vs 200 | 52 vs 52 | 75 | 42 vs 50 ≥ n-CR (< .1) | 25 vs 30 (10% vs 20% @ 7 y) (< .03) | 48 vs 58 (21% vs 42% @ 7 y) (.01) |
| Cavo et al51 BOLOGNA 96 | Before treatment | VAD × 4 → CTX → MEL 200 vs VAD × 4 → CTX → MEL 200; MEL 120 + busulfan | 110 vs 110 | 53 vs 53 | 38 | 21 vs 24 NS | 25 vs 34 NA (< .05) | 56 vs 60 NS |
| Fermand et al53 MAG 95 | Before treatment | DEX × 2 → CTX → VAD × 3-4 → MEL 140 + VP16 + CTX + TBI 12 Gy vs DEX × 2 → CTX → VAD × 3-4 → MEL 140; MEL 140 + VP16 + TBI 12 Gy | 97 vs 96 | 50 vs 50 | 53 | 39 vs 37 NS | 31 vs 33 NS | 49 vs 73 NA (.14) |
| Segeren et al52 HOVON* (intermediate dose therapy) | After VAD ± response | VAD × 3-4 → CTX → MEL 70 × 2 vs VAD × 3-4 → CTX → MEL 70 × 2 → CTX + TBI 9 Gy | 129 vs 132 | 55 vs 56 | 40 | 14 vs 28 (.004) | NA (15% vs 29% @ 4 y) (< .03) | NA (55% vs 50% @ 4 y) (< .3) |
| Standard-dose therapy vs tandem transplantation | ||||||||
| Barlogie et al43 SWOG vs TT I* | Historical controls | VMCB (P)/VBAP (P)/VAD vs VAD × 2-3 → CTX → EDAP → MEL 200 × 2 (< PR, MEL 140 + TBI 8.5 Gy) | 152 vs 152 | 52 vs 52 | 114 | NA vs 41 | 16 vs 37 (5% vs 15% @ 10 y) (< .0001) | 43 vs 79 (15% vs 33% @ 10 y) (< .0001) |
Study . | Randomization . | Regimens . | N . | Mean age, y . | Median FU, mo . | % CR (P) . | EFS, median mo. (P) . | OS, median mo. (P) . |
|---|---|---|---|---|---|---|---|---|
| Standard-dose therapy vs high-dose therapy | ||||||||
| Attal et al8 IFM 90* | Before treatment | VMCP/BVAP × 18 vs VMCP/BVAP × 4-6 → CTX + MEL 140 + TBI 8 Gy | 100 vs 100 | 58 vs 57 | 108 | 14 vs 38 (< .001) | 18 vs 28 (.01) | 44 vs 57 (20% vs 35% @ 7 y) (.03) |
| Child et al16 MRC VII* | Before treatment | ABCM × 4-12 vs CVAMP × 3 → CTX + MEL 200 | 200 vs 201 | 56 vs 55 | 42 | 8 vs 44 (< .001) | 20 vs 32 (16% vs 36% @ 4 y) (< .001) | 42 vs 54 (46% vs 55% @ 4 y) (.04) |
| Blade et al50 PETHEMA† | Responders to induction | ABCM/VBAD × 12 vs ABCM/VBAD × 4 → MEL 200 | 83 vs 81 | 56 vs 56 | 66 | 11 vs 30 (< .002) | 34 vs 43 NA | 67 vs 65 NA |
| Single transplantation vs tandem transplantation | ||||||||
| Attal et al15 IFM 94* | Before treatment | VAD × 3-4 → G-CSF→ MEL 140 + TBI 8 Gy vs VAD × 3-4 → G-CSF→ MEL 140; MEL 140 + TBI 8 Gy | 199 vs 200 | 52 vs 52 | 75 | 42 vs 50 ≥ n-CR (< .1) | 25 vs 30 (10% vs 20% @ 7 y) (< .03) | 48 vs 58 (21% vs 42% @ 7 y) (.01) |
| Cavo et al51 BOLOGNA 96 | Before treatment | VAD × 4 → CTX → MEL 200 vs VAD × 4 → CTX → MEL 200; MEL 120 + busulfan | 110 vs 110 | 53 vs 53 | 38 | 21 vs 24 NS | 25 vs 34 NA (< .05) | 56 vs 60 NS |
| Fermand et al53 MAG 95 | Before treatment | DEX × 2 → CTX → VAD × 3-4 → MEL 140 + VP16 + CTX + TBI 12 Gy vs DEX × 2 → CTX → VAD × 3-4 → MEL 140; MEL 140 + VP16 + TBI 12 Gy | 97 vs 96 | 50 vs 50 | 53 | 39 vs 37 NS | 31 vs 33 NS | 49 vs 73 NA (.14) |
| Segeren et al52 HOVON* (intermediate dose therapy) | After VAD ± response | VAD × 3-4 → CTX → MEL 70 × 2 vs VAD × 3-4 → CTX → MEL 70 × 2 → CTX + TBI 9 Gy | 129 vs 132 | 55 vs 56 | 40 | 14 vs 28 (.004) | NA (15% vs 29% @ 4 y) (< .03) | NA (55% vs 50% @ 4 y) (< .3) |
| Standard-dose therapy vs tandem transplantation | ||||||||
| Barlogie et al43 SWOG vs TT I* | Historical controls | VMCB (P)/VBAP (P)/VAD vs VAD × 2-3 → CTX → EDAP → MEL 200 × 2 (< PR, MEL 140 + TBI 8.5 Gy) | 152 vs 152 | 52 vs 52 | 114 | NA vs 41 | 16 vs 37 (5% vs 15% @ 10 y) (< .0001) | 43 vs 79 (15% vs 33% @ 10 y) (< .0001) |
FU indicates follow-up; CTX, cyclophosphamide; PETHEMA, Programa para el Estudio de la Therapéutica en Hemopatía Maligna; G-CSF, granulocyte colony-stimulating factor; MAG, Myélomo Autogreffe; HOVON, Stichting Hemato-Oncologie voor Volwassen Nederland; MEL, melphalan; DEX, dexamethasone; and MRC, Medical Research Council.
IFN maintenance therapy.
IFN and DEX maintenance therapy.