Key phase 3 studies of bortezomib-based combinations as frontline therapy in patients ineligible or eligible for stem cell transplantation
| Study . | Regimen . | N . | Response rates, % . | . | Outcomes, % . | Grade ≥ 3 PN, % . |
|---|---|---|---|---|---|---|
| Studies in transplant-ineligible patients of VMP-based regimens | ||||||
| VISTA59,61 | VMP | 344 | ORR: 71 | TTP: 24.0 mo | 13 | |
| CR: 30 | OS: 56.4 mo | |||||
| MP | 338 | ORR: 35 | TTP: 16.6 mo | 0 | ||
| CR: 4 | OS: 43.1 mo | |||||
| GEM05MAS6540,62 | VMP induction | 130 | Postinduction: | PFS: 34 mo | 7 | |
| ORR: 80 | 3-y OS: 74 | |||||
| CR/nCR: 32 | ||||||
| VTP induction | 130 | Postinduction: | PFS: 25 mo | 9 | ||
| ORR: 81 | 3-y OS: 65 | |||||
| CR/nCR: 36 | ||||||
| Second randomization | VT maintenance | 91 | Postmaintenance: | PFS: 39 mo | 9 | |
| ORR: 95 | 5-y OS: 69 | |||||
| CR/nCR: 56 | ||||||
| VP maintenance | 87 | Postmaintenance: | PFS: 32 mo | 3 | ||
| ORR: 97 | OS: 60 mo | |||||
| CR/nCR: 50 | ||||||
| GIMEMA-MM-03–0539,41 | VMPT-VT | 254 | ORR: 89 | 3-y PFS: 56 | 8 | |
| CR: 38 | 3-y TTNT: 72 | |||||
| 3-y OS: 89 | ||||||
| VMP | 257 | ORR: 81 | 3-y PFS: 41 | 5 | ||
| CR: 24 | 3-y TTNT: 60 | |||||
| 3-y OS: 87 | ||||||
| Weekly btz | 372 | ORR: 85 | 3-y PFS: 50 | 3 | ||
| CR: 30 | 3-y TTNT: 72 | |||||
| 3-y OS: 88 | ||||||
| Twice-weekly btz | 139 | ORR: 86 | 3-y PFS: 47 | 16 | ||
| CR: 35 | 3-y TTNT: 61 | |||||
| 3-y OS: 89 | ||||||
| UPFRONT community-based phase 3b99 | VD + btz maintenance | 168 | ORR: 73 | PFS: 14.3 mo | Induction: 19; maintenance: 6 | |
| ≥ VGPR: 37 | 2-y OS: 73.7 | |||||
| CR/nCR: 30 | ||||||
| VTD + btz maintenance | 167 | ORR: 80 | PFS: 14.9 mo | Induction: 24; maintenance: 7 | ||
| ≥ VGPR: 51 | 2-y OS: 73.6 | |||||
| CR/nCR: 40 | ||||||
| VMP + btz maintenance | 167 | ORR: 69 | PFS: 17.3 mo | Induction: 19; maintenance: 3 | ||
| ≥ VGPR: 40 | 2-y OS: 77.6 | |||||
| CR/nCR: 33 | ||||||
| Studies of bortezomib-based induction therapy in transplant-eligible patients | ||||||
| IFM2005-0166 | VD | 240 | Postinduction: | Posttransplant: | PFS: 36.0 mo | 9.2 |
| ORR: 78.5 | ≥ VGPR: 54.3 | 3-y OS: 81.4 | ||||
| ≥ VGPR: 37.7 | CR/nCR: 35.0 | |||||
| CR/nCR: 14.8 | ||||||
| VAD | 242 | Postinduction: | Posttransplant: | PFS: 20.7 mo | 2.5 | |
| ORR: 62.8 | ≥ VGPR: 37.2 | 3-y OS: 77.4 | ||||
| ≥ VGPR: 15.1 | CR/nCR: 18.4 | |||||
| CR/nCR: 6.4 | ||||||
| GIMEMA study72,82 | VTD induction and consolidation | 241 | Postinduction: | Posttransplant: | 3-y PFS: 68 | 10 |
| (160 per-protocol) | ORR: 93 | ≥ VGPR: 79 | 3-y OS: 86 | During consolidation (per-protocol): 0.6 | ||
| ≥ VGPR: 62 | CR/nCR: 52 | Postconsolidation (per-protocol): | ||||
| CR/nCR: 31 | Postconsolidation (per-protocol): | 3-y TTP: 61 | ||||
| ORR: 98 | 3-y PFS: 60 | |||||
| ≥ VGPR: 92 | ||||||
| CR/nCR: 73 | ||||||
| TD induction and consolidation | 239 | Postinduction: | Posttransplant: | 3-y PFS: 56 | 2 | |
| (161 per-protocol) | ORR: 79 | ≥ VGPR: 58 | 3-y OS: 84 | During consolidation (per-protocol): 0 | ||
| ≥ VGPR: 28 | CR/nCR: 31 | Postconsolidation (per-protocol): | ||||
| CR/nCR: 11 | Postconsolidation (per-protocol): | 3-y TTP: 48 | ||||
| ORR: 99 | 3-y PFS: 48 | |||||
| ≥ VGPR: 88 | ||||||
| CR/nCR: 61 | ||||||
| GEM05-MENOS6574,84 | VTD induction | 130 | Postinduction: | Posttransplant: | NR | 12 |
| ORR: 85 | ≥ VGPR: 65 | |||||
| ≥ VGPR: 60 | CR/nCR: 46 | |||||
| CR/nCR: 35 | ||||||
| TD induction | 127 | Postinduction: | Posttransplant: | NR | 1 | |
| ORR: 64 | ≥ VGPR: 40 | |||||
| ≥ VGPR: 29 | CR/nCR: 24 | |||||
| CR/nCR: 14 | ||||||
| Chemo-btz induction | 129 | Postinduction: | Posttransplant: | NR | 1 | |
| ORR: 75 | ≥ VGPR: 51 | |||||
| ≥ VGPR: 36 | CR/nCR: 38 | |||||
| CR/nCR: 21 | ||||||
| Second randomization | VT maintenance | 90 | Increase in: | NR | 12 | |
| CR: 23 | ||||||
| VGPR: 1 | ||||||
| Thalidomide maintenance | 89 | Increase in: | NR | 10 | ||
| CR: 11 | ||||||
| VGPR: 5 | ||||||
| IFN-α maintenance | 87 | Increase in: | NR | 0 | ||
| CR: 19 | ||||||
| VGPR: 3 | ||||||
| IFM2007-0273 | vTD | 100 | Postinduction: | Posttransplant: | PFS: 26 mo | 3 |
| ORR: 88 | ≥ VGPR: 74 | |||||
| ≥ VGPR: 49 | CR/nCR: 61 | |||||
| CR/nCR: 31 | ||||||
| VD | 99 | Postinduction: | Posttransplant: | PFS: 30 mo | 11 | |
| ORR: 81 | ≥ VGPR: 58 | |||||
| ≥ VGPR: 36 | CR/nCR: 52 | |||||
| CR/nCR: 22 | ||||||
| HOVON-65/GMMG-HD475 | PAD induction/bortezomib maintenance | 371/205 | Postinduction: | Posttransplant: | PFS: 36 mo | 26 |
| ORR: 78 | ≥ VGPR: 61 | 3-y OS: 78 | ||||
| ≥ VGPR: 42 | CR/nCR: 30 | |||||
| CR/nCR: 11 | Improvements during maintenance: | |||||
| < CR to CR: 12 | ||||||
| < nCR to nCR: 13 | ||||||
| < VGPR to VGPR: 11 | ||||||
| < PR to PR: 1 | ||||||
| Overall: | ||||||
| ORR: 91 | ||||||
| ≥ VGPR: 76 | ||||||
| CR/nCR: 49 | ||||||
| VAD induction/thalidomide maintenance | 373/239 | Postinduction: | Posttransplant: | PFS: 27 mo | 12 | |
| ORR: 77 | ≥ VGPR: 36 | 3-y OS: 70 | ||||
| ≥ VGPR: 15 | CR/nCR: 15 | |||||
| CR/nCR: 5 | Improvements during maintenance: | |||||
| < CR to CR: 10 | ||||||
| < nCR to nCR: 12 | ||||||
| < VGPR to VGPR: 13 | ||||||
| < PR to PR: 4 | ||||||
| Overall: | ||||||
| ORR: 83 | ||||||
| ≥ VGPR: 55 | ||||||
| CR/nCR: 34 |
| Study . | Regimen . | N . | Response rates, % . | . | Outcomes, % . | Grade ≥ 3 PN, % . |
|---|---|---|---|---|---|---|
| Studies in transplant-ineligible patients of VMP-based regimens | ||||||
| VISTA59,61 | VMP | 344 | ORR: 71 | TTP: 24.0 mo | 13 | |
| CR: 30 | OS: 56.4 mo | |||||
| MP | 338 | ORR: 35 | TTP: 16.6 mo | 0 | ||
| CR: 4 | OS: 43.1 mo | |||||
| GEM05MAS6540,62 | VMP induction | 130 | Postinduction: | PFS: 34 mo | 7 | |
| ORR: 80 | 3-y OS: 74 | |||||
| CR/nCR: 32 | ||||||
| VTP induction | 130 | Postinduction: | PFS: 25 mo | 9 | ||
| ORR: 81 | 3-y OS: 65 | |||||
| CR/nCR: 36 | ||||||
| Second randomization | VT maintenance | 91 | Postmaintenance: | PFS: 39 mo | 9 | |
| ORR: 95 | 5-y OS: 69 | |||||
| CR/nCR: 56 | ||||||
| VP maintenance | 87 | Postmaintenance: | PFS: 32 mo | 3 | ||
| ORR: 97 | OS: 60 mo | |||||
| CR/nCR: 50 | ||||||
| GIMEMA-MM-03–0539,41 | VMPT-VT | 254 | ORR: 89 | 3-y PFS: 56 | 8 | |
| CR: 38 | 3-y TTNT: 72 | |||||
| 3-y OS: 89 | ||||||
| VMP | 257 | ORR: 81 | 3-y PFS: 41 | 5 | ||
| CR: 24 | 3-y TTNT: 60 | |||||
| 3-y OS: 87 | ||||||
| Weekly btz | 372 | ORR: 85 | 3-y PFS: 50 | 3 | ||
| CR: 30 | 3-y TTNT: 72 | |||||
| 3-y OS: 88 | ||||||
| Twice-weekly btz | 139 | ORR: 86 | 3-y PFS: 47 | 16 | ||
| CR: 35 | 3-y TTNT: 61 | |||||
| 3-y OS: 89 | ||||||
| UPFRONT community-based phase 3b99 | VD + btz maintenance | 168 | ORR: 73 | PFS: 14.3 mo | Induction: 19; maintenance: 6 | |
| ≥ VGPR: 37 | 2-y OS: 73.7 | |||||
| CR/nCR: 30 | ||||||
| VTD + btz maintenance | 167 | ORR: 80 | PFS: 14.9 mo | Induction: 24; maintenance: 7 | ||
| ≥ VGPR: 51 | 2-y OS: 73.6 | |||||
| CR/nCR: 40 | ||||||
| VMP + btz maintenance | 167 | ORR: 69 | PFS: 17.3 mo | Induction: 19; maintenance: 3 | ||
| ≥ VGPR: 40 | 2-y OS: 77.6 | |||||
| CR/nCR: 33 | ||||||
| Studies of bortezomib-based induction therapy in transplant-eligible patients | ||||||
| IFM2005-0166 | VD | 240 | Postinduction: | Posttransplant: | PFS: 36.0 mo | 9.2 |
| ORR: 78.5 | ≥ VGPR: 54.3 | 3-y OS: 81.4 | ||||
| ≥ VGPR: 37.7 | CR/nCR: 35.0 | |||||
| CR/nCR: 14.8 | ||||||
| VAD | 242 | Postinduction: | Posttransplant: | PFS: 20.7 mo | 2.5 | |
| ORR: 62.8 | ≥ VGPR: 37.2 | 3-y OS: 77.4 | ||||
| ≥ VGPR: 15.1 | CR/nCR: 18.4 | |||||
| CR/nCR: 6.4 | ||||||
| GIMEMA study72,82 | VTD induction and consolidation | 241 | Postinduction: | Posttransplant: | 3-y PFS: 68 | 10 |
| (160 per-protocol) | ORR: 93 | ≥ VGPR: 79 | 3-y OS: 86 | During consolidation (per-protocol): 0.6 | ||
| ≥ VGPR: 62 | CR/nCR: 52 | Postconsolidation (per-protocol): | ||||
| CR/nCR: 31 | Postconsolidation (per-protocol): | 3-y TTP: 61 | ||||
| ORR: 98 | 3-y PFS: 60 | |||||
| ≥ VGPR: 92 | ||||||
| CR/nCR: 73 | ||||||
| TD induction and consolidation | 239 | Postinduction: | Posttransplant: | 3-y PFS: 56 | 2 | |
| (161 per-protocol) | ORR: 79 | ≥ VGPR: 58 | 3-y OS: 84 | During consolidation (per-protocol): 0 | ||
| ≥ VGPR: 28 | CR/nCR: 31 | Postconsolidation (per-protocol): | ||||
| CR/nCR: 11 | Postconsolidation (per-protocol): | 3-y TTP: 48 | ||||
| ORR: 99 | 3-y PFS: 48 | |||||
| ≥ VGPR: 88 | ||||||
| CR/nCR: 61 | ||||||
| GEM05-MENOS6574,84 | VTD induction | 130 | Postinduction: | Posttransplant: | NR | 12 |
| ORR: 85 | ≥ VGPR: 65 | |||||
| ≥ VGPR: 60 | CR/nCR: 46 | |||||
| CR/nCR: 35 | ||||||
| TD induction | 127 | Postinduction: | Posttransplant: | NR | 1 | |
| ORR: 64 | ≥ VGPR: 40 | |||||
| ≥ VGPR: 29 | CR/nCR: 24 | |||||
| CR/nCR: 14 | ||||||
| Chemo-btz induction | 129 | Postinduction: | Posttransplant: | NR | 1 | |
| ORR: 75 | ≥ VGPR: 51 | |||||
| ≥ VGPR: 36 | CR/nCR: 38 | |||||
| CR/nCR: 21 | ||||||
| Second randomization | VT maintenance | 90 | Increase in: | NR | 12 | |
| CR: 23 | ||||||
| VGPR: 1 | ||||||
| Thalidomide maintenance | 89 | Increase in: | NR | 10 | ||
| CR: 11 | ||||||
| VGPR: 5 | ||||||
| IFN-α maintenance | 87 | Increase in: | NR | 0 | ||
| CR: 19 | ||||||
| VGPR: 3 | ||||||
| IFM2007-0273 | vTD | 100 | Postinduction: | Posttransplant: | PFS: 26 mo | 3 |
| ORR: 88 | ≥ VGPR: 74 | |||||
| ≥ VGPR: 49 | CR/nCR: 61 | |||||
| CR/nCR: 31 | ||||||
| VD | 99 | Postinduction: | Posttransplant: | PFS: 30 mo | 11 | |
| ORR: 81 | ≥ VGPR: 58 | |||||
| ≥ VGPR: 36 | CR/nCR: 52 | |||||
| CR/nCR: 22 | ||||||
| HOVON-65/GMMG-HD475 | PAD induction/bortezomib maintenance | 371/205 | Postinduction: | Posttransplant: | PFS: 36 mo | 26 |
| ORR: 78 | ≥ VGPR: 61 | 3-y OS: 78 | ||||
| ≥ VGPR: 42 | CR/nCR: 30 | |||||
| CR/nCR: 11 | Improvements during maintenance: | |||||
| < CR to CR: 12 | ||||||
| < nCR to nCR: 13 | ||||||
| < VGPR to VGPR: 11 | ||||||
| < PR to PR: 1 | ||||||
| Overall: | ||||||
| ORR: 91 | ||||||
| ≥ VGPR: 76 | ||||||
| CR/nCR: 49 | ||||||
| VAD induction/thalidomide maintenance | 373/239 | Postinduction: | Posttransplant: | PFS: 27 mo | 12 | |
| ORR: 77 | ≥ VGPR: 36 | 3-y OS: 70 | ||||
| ≥ VGPR: 15 | CR/nCR: 15 | |||||
| CR/nCR: 5 | Improvements during maintenance: | |||||
| < CR to CR: 10 | ||||||
| < nCR to nCR: 12 | ||||||
| < VGPR to VGPR: 13 | ||||||
| < PR to PR: 4 | ||||||
| Overall: | ||||||
| ORR: 83 | ||||||
| ≥ VGPR: 55 | ||||||
| CR/nCR: 34 |
PN rates in IFM2005-01 shown through induction and first transplantation. PN rates in HOVON-65/GMMG-HD4 shown through all protocol treatment, including bortezomib or thalidomide maintenance.
VISTA indicates VELCADE as Initial Standard Therapy in multiple myeloma: Assessment with melphalan and prednisone; TTNT, time to next therapy; Chemo-btz, complex chemotherapy regimen followed by bortezomib; VD, bortezomib-dexamethasone; NR, not reported; and PAD, bortezomib-doxorubicin-dexamethasone.