Table 2.
Clinical trial experience with bortezomib in lymphoma
| Reference | Study | Evaluable Patients | ORR (CR + PR) |
|---|---|---|---|
| Treatment-naïve MCL | |||
| Kahl et al 2008 [20] | Phase II, single-arm, VcR-CVAD followed by maintenance rituximab therapy | N = 30 | 90% |
| Relapsed/refractory MCL (and other lymphomas) | |||
| O'Connor et al 2005 [21] | Phase II, single-arm, monotherapy (1.5 mg/m2 days 1, 4, 8, 11 every 21 days) | N = 24: MCL (n = 10), follicular lymphoma (n = 9), small lymphocytic lymphoma or CLL (n = 3), marginal zone lymphoma (n = 2) | MCL 50% Follicular lymphoma 78% Small lymphocytic lymphoma or CLL 0% Marginal zone lymphoma 100% |
| Gerecitano et al 2009 [22] | Extension of O'Connor et al 2005 trial: continuing patients switched to weekly bortezomib 1.8 mg/m2 | N = 22: MCL (n = 8), follicular lymphoma (n = 14) | MCL 25% Follicular lymphoma 14% |
| Goy et al 2005 [23] | Phase II, single-arm, monotherapy (1.5 mg/m2 days 1, 4, 8, 11 every 21 days) | N = 50: MCL (n = 29), other B-cell lymphomas (n = 21) | MCL 41% Other B-cell lymphomas 19% |
| Strauss et al 2006 [24] | Phase II, single-arm, monotherapy (1.3 mg/m2 days 1, 4, 8, 11 every 21 days) | N = 48: MCL (n = 24), follicular lymphoma (n = 11), other lymphomas (n = 13) | MCL 29% Follicular lymphoma 18% Others 23% |
| Relapsed/refractory MCL | |||
| PINNACLE, Fisher et al 2006 [25] | Phase II, single-arm, monotherapy (1.3 mg/m2 days 1, 4, 8, 11 every 21 days) | N = 141 | 33% |
| Updated PINNACLE,a Goy et al 2009 [26] | Phase II, single-arm, monotherapy (1.3 mg/m2 days 1, 4, 8, 11 every 21 days) | N = 55 | 29% |
| Belch et al 2007 [27] | Phase II, single-arm, monotherapy (1.3 mg/m2 days 1, 4, 8, 11 every 21 days) | N = 28 | 46% |
| O'Connor et al 2009 [28] | Phase II, single-arm monotherapy (1.5 mg/m2 days 1, 4, 8, 11 every 21 days) | N = 36b | 47% |
| Weigert et al 2009 [29] | Multicenter observational study of R-HAD+B salvage regimen: - bortezomib (1.5 mg/m2 days 1, 4) - cytarabine (2,000 mg/m2 days 2, 3c) - dexamethasone (40 mg days 1-4) - Rituximab (375 mg/m2 on day 0 for patients not refractory to prior rituximab-containing regimens) |
N = 8 | 50% |
| DLBCL | |||
| Dunleavy et al 2009 [30] | Phase I/II, 2-part study of bortezomib monotherapy (part A) followed by bortezomib plus DA-EPOCH (part B) | N = 47 (n = 23 part A, n = 44 part B) | Part A 4% Part B 34% |
| Relapsed/refractory Hodgkin lymphoma | |||
| Trelle et al 2007 [31] | Phase II, bortezomib (1.3 mg/m2) plus dexamethasone (20 mg) on days 1, 4, 8, 11 every 21 days | N = 12 | 0% (17% SD, 83% PD) |
| Blum et al 2007 [32] | Phase II, single-arm, monotherapy (1.3 mg/m2 on days 1, 4, 8, 11 every 21 days) | N = 29 | 0% (30% SD, 70% PD) |
| Mendler et al 2008 [33] | Phase II, single-arm bortezomib (1 mg/m2 on days 1, 4, 8, 11) and gemcitabine (800 mg/m2 on days 1, 8) every 21 days | N = 18 | 22% |
Abbreviations: MCL - mantle-cell lymphoma, ORR - overall response rate, CR - complete response, PR - partial response, CLL - chronic lymphocytic leukemia, DLBCL - diffuse large B-cell lymphoma, DA-EPOCH - doxorubicin-based chemotherapy (etoposide, vincristine, doxorubicin, with cyclophosphamide and prednisone), R-HAD+B - bortezomib, high-dose cytarabine, dexamethasone, SD - stable disease, PD - progressive disease; VcR-CVAD - bortezomib, rituximab, cyclophosphamide, doxorubicin, vincristine and dexamethasone.
aOriginal PINNACLE publication reported data from median follow-up period of 13.4 months [25]; updated publication described data from median follow-up of 26.4 months [26]
bThe 36 evaluable patients included 11 patients whose outcome was reported by O'Connor et al 2005 [21,28]
cPatients ≥60 years of age were treated with 1,000 mg/m2 [29]