Table 2.
Bortezomib-based combination therapies in mantle cell lymphoma.
| Ref. | Prior therapies | Bortezomib combination studied | Bortezomib dose and schedule | Phase | No. of patients | Results |
|---|---|---|---|---|---|---|
| [79] | None | VcR-CVAD × 6 with consolidation and MR in responders | 1.3 mg/m2 (days 1 and 4 every 21 days; first 7 patients received 1.5 mg/m2) | II | 30 | 90% ORR, 77% CR/CRu, 3-year PFS 63% and OS 86% after median f/u of 42 months |
| [80] | None | VcR-CVAD × 6 followed by ASCT or MR in responders | 1.3 mg/m2 (days 1 and 4 every 21 days) | II | 75 | 95% ORR, 68% CRs, 3-year PFS 72% and OS 88% after median f/u of 4.5 years |
| [81] | None | VcR-CHOP × 6 | 0.7, 1.0 or 1.3 mg/m2 (days 1 and 4 every 21 days) | I/II | 76 (40 DLBCL + 36 MCL) | MCL: evaluable ORR 91%, 72% CR/CRu; ITT ORR 81%, 64% CR/CRu; 2-year PFS 44% and OS 86% |
| [128] | 1 – 3 prior therapies | Bortezomib + gemcitabine (1000 mg/m2 on days 1, 8) | 1.0 mg/m2 (days 1, 4, 8, 11 every 21 days) | II | 26 | 60% ORR, 11.5% CRs, median PFS 11.4 months |
| [129] | Median 3 prior therapies | BDR × 6 with 4 doses of rituximab consolidation in responders* | 1.3 mg/m2 (days 1, 4, 8, 11 every 21 days) | II | 16 | 81.3% ORR, 43.8% CRs, median PFS 12.1 and OS 38.6 months |
| [130] | None | RiPAD + C × 6 (in responders; nonresponders received 4 cycles) | 1.3 mg/m2 (days 1, 4, 8, 11 every 35 days) | II | 39 | 79% ORR, 59% CRs, median PFS 26 months and OS not reached at 27 months |
| [90] | 2 | Bortezomib + vorinostat | 1.3 mg/m2 (days 1, 4, 8, 11 every 21 days) | II | 47 (26 DLBCL + 21 MCL) | MCL: 47% ORR, 12% CRs (all in bortezomib-naïve cohort) |
Rituximab given at a dose of 375 mg/m2 on day 1 and dexamethasone given at a dose of 40 mg orally on days 1 – 4.
ASCT: Autologous stem cell transplant; BDR: Bortezomib, dexamethasone, rituximab; CR: Complete response; CRu: Unconfirmed complete response; DLBCL: Diffuse large B-cell lymphoma; f/u: Follow up; ITT: Intention to treat; MCL: Mantle cell lymphoma; MR: Maintenance rituximab; ORR: Overall response rate; OS: Overall survival; PFS: Progression-free survival; RiPAD + C: Rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil; VcR-CHOP: Bortezomib, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; VcR-CVAD: Rituximab, bortezomib, modified hyperfractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone.