Key studies of bortezomib in relapsed/refractory MM
| Study . | Regimen* . | N . | ORR,† % . | CR/nCR, % . | Outcomes . | Common grade ≥ 3 AEs, % . |
|---|---|---|---|---|---|---|
| Phase 2 SUMMIT27,98 | Btz ± dex | 202 | ≥ MR: 35 | 10 | DOR: 12.7 mo | Thrombocytopenia 31; neutropenia 14; PN 12; fatigue 12; diarrhea 8; vomiting 8; anemia 8 |
| ≥ PR: 27 | TTP: 7 mo | |||||
| OS: 17 mo | ||||||
| Phase 2 CREST28,29 | Btz 1.0 (± dex) | 28 | ≥ MR: 33 (44) | 11 (19) | DOR: 9.5 mo | Thrombocytopenia 29; neutropenia 11; lymphopenia 11; hyponatremia 11; limb pain 11; PN 8 |
| ≥ PR: 30 (37) | TTP: 7.0 mo | |||||
| OS: 26.8 mo | ||||||
| Btz 1.3 ± dex | 26 | ≥ MR: 50 (62) | 4 (4) | DOR: 13.7 mo | Thrombocytopenia 23; neutropenia 23; pneumonia 15; PN 15; lymphopenia 12; weakness 12; limb pain 8; hyponatremia 8 | |
| ≥ PR: 38 (50) | TTP: 11.0 mo | |||||
| OS: 60 mo | ||||||
| Phase 3 APEX30,31 | Btz | 333 | 43 | 15 | DOR: 7.8 mo | Thrombocytopenia 30; neutropenia 14; anemia 10; PN 8; diarrhea 7 |
| TTP: 6.2 mo | ||||||
| OS: 29.8 mo | ||||||
| Dex | 336 | 18 | 2 | DOR: 5.6 mo | Anemia 11; thrombocytopenia 6; diarrhea 2; PN 1; neutropenia 1 | |
| TTP: 3.5 mo | ||||||
| OS: 23.7 mo | ||||||
| Phase 3 MMY-302142 | SC Btz | 148 | 52 | 20 | DOR: 9.7 mo | Neutropenia 18; thrombocytopenia 13; anemia 12; leucopenia 6; sensory PN 5; pneumonia 5; neuralgia 3 |
| TTP: 10.4 mo | ||||||
| PFS: 10.2 mo | ||||||
| 1-y OS: 73 | ||||||
| IV Btz | 74 | 52 | 22 | DOR: 8.7 mo | Thrombocytopenia 19; neutropenia 18; sensory PN 15; neuralgia 9; anemia 8; pneumonia 8; leucopenia 7 | |
| TTP: 9.4 mo | ||||||
| PFS: 8.0 mo | ||||||
| 1-y OS: 77 | ||||||
| Phase 3 MMY-300150 | Btz + PLD | 324 | 44 | 13 | TTP: 9.3 mo | Neutropenia 29; thrombocytopenia 23; anemia 9; diarrhea 7; asthenia 6; PN 4 |
| PFS: 9.0 mo | ||||||
| 15-mo OS: 76 | ||||||
| Btz | 322 | 41 | 10 | TTP: 6.5 mo | Thrombocytopenia 16; neutropenia 15; anemia 9; PN 9; diarrhea 4; asthenia 3 | |
| PFS: 6.5 mo | ||||||
| 15-mo OS: 65 | ||||||
| Phase 3 IFM/EBMT54 | VTD | 135 | 90 | 30 | TTP: 19.5 mo | Thrombocytopenia 16; thromboembolic events 7 |
| PFS: 18.6 mo | ||||||
| 2-y OS: 72 | ||||||
| TD | 132 | 69 | 12 | TTP: 13.8 mo | Thrombocytopenia 7; thromboembolic events 5 | |
| PFS: 12.7 mo | ||||||
| 2-y OS: 68 |
| Study . | Regimen* . | N . | ORR,† % . | CR/nCR, % . | Outcomes . | Common grade ≥ 3 AEs, % . |
|---|---|---|---|---|---|---|
| Phase 2 SUMMIT27,98 | Btz ± dex | 202 | ≥ MR: 35 | 10 | DOR: 12.7 mo | Thrombocytopenia 31; neutropenia 14; PN 12; fatigue 12; diarrhea 8; vomiting 8; anemia 8 |
| ≥ PR: 27 | TTP: 7 mo | |||||
| OS: 17 mo | ||||||
| Phase 2 CREST28,29 | Btz 1.0 (± dex) | 28 | ≥ MR: 33 (44) | 11 (19) | DOR: 9.5 mo | Thrombocytopenia 29; neutropenia 11; lymphopenia 11; hyponatremia 11; limb pain 11; PN 8 |
| ≥ PR: 30 (37) | TTP: 7.0 mo | |||||
| OS: 26.8 mo | ||||||
| Btz 1.3 ± dex | 26 | ≥ MR: 50 (62) | 4 (4) | DOR: 13.7 mo | Thrombocytopenia 23; neutropenia 23; pneumonia 15; PN 15; lymphopenia 12; weakness 12; limb pain 8; hyponatremia 8 | |
| ≥ PR: 38 (50) | TTP: 11.0 mo | |||||
| OS: 60 mo | ||||||
| Phase 3 APEX30,31 | Btz | 333 | 43 | 15 | DOR: 7.8 mo | Thrombocytopenia 30; neutropenia 14; anemia 10; PN 8; diarrhea 7 |
| TTP: 6.2 mo | ||||||
| OS: 29.8 mo | ||||||
| Dex | 336 | 18 | 2 | DOR: 5.6 mo | Anemia 11; thrombocytopenia 6; diarrhea 2; PN 1; neutropenia 1 | |
| TTP: 3.5 mo | ||||||
| OS: 23.7 mo | ||||||
| Phase 3 MMY-302142 | SC Btz | 148 | 52 | 20 | DOR: 9.7 mo | Neutropenia 18; thrombocytopenia 13; anemia 12; leucopenia 6; sensory PN 5; pneumonia 5; neuralgia 3 |
| TTP: 10.4 mo | ||||||
| PFS: 10.2 mo | ||||||
| 1-y OS: 73 | ||||||
| IV Btz | 74 | 52 | 22 | DOR: 8.7 mo | Thrombocytopenia 19; neutropenia 18; sensory PN 15; neuralgia 9; anemia 8; pneumonia 8; leucopenia 7 | |
| TTP: 9.4 mo | ||||||
| PFS: 8.0 mo | ||||||
| 1-y OS: 77 | ||||||
| Phase 3 MMY-300150 | Btz + PLD | 324 | 44 | 13 | TTP: 9.3 mo | Neutropenia 29; thrombocytopenia 23; anemia 9; diarrhea 7; asthenia 6; PN 4 |
| PFS: 9.0 mo | ||||||
| 15-mo OS: 76 | ||||||
| Btz | 322 | 41 | 10 | TTP: 6.5 mo | Thrombocytopenia 16; neutropenia 15; anemia 9; PN 9; diarrhea 4; asthenia 3 | |
| PFS: 6.5 mo | ||||||
| 15-mo OS: 65 | ||||||
| Phase 3 IFM/EBMT54 | VTD | 135 | 90 | 30 | TTP: 19.5 mo | Thrombocytopenia 16; thromboembolic events 7 |
| PFS: 18.6 mo | ||||||
| 2-y OS: 72 | ||||||
| TD | 132 | 69 | 12 | TTP: 13.8 mo | Thrombocytopenia 7; thromboembolic events 5 | |
| PFS: 12.7 mo | ||||||
| 2-y OS: 68 |
SUMMIT indicates Study of Uncontrolled Multiple Myeloma managed with proteasome Inhibition Therapy; Btz, bortezomib; dex, dexamethasone; DOR, duration of response; CREST, Clinical Response and Efficacy Study of bortezomib in the Treatment of relapsing multiple myeloma; and APEX, Assessment of Proteasome inhibition for Extending remissions.
Bortezomib dosed at 1.3 mg/m2 (or 1.0 mg/m2 where stated) on days 1, 4, 8, and 11 for 8 21-day cycles. In APEX/the IFM/EBMT studies, patients could also receive three 5-week/four 6-week cycles of bortezomib 1.3 mg/m2 on days 1, 8, 15, and 22.
More than or equal to PR unless stated.