Efficacy of selected regimens
| Regimen . | Patients, n . | Schedule . | CR, % . | PFS/EFS/TTP, % . | OS, % . |
|---|---|---|---|---|---|
| Stem cell transplantation | |||||
| BD | 121 | B: 1.3 mg/m2 days 1, 4, 8, 11; D: 40 mg days 1-4 (cycles 1-4), days 9-12 (cycles 1-2); for four 21-d cycles | 6 | 50 at 36 mo | 81 at 36 mo |
| Mel 20017 | Mel 200: 200 mg/m2 (double if < VGPR) | 39 ≥ nCR | |||
| PAD induction | 413 | P: 1.3 mg/m2 days 1, 4, 8, 11; A: 9 mg/m2 days 1-4; D: 40 mg days 1-4, 9-12, 17-20; for three 28-d cycles | 7 | 50 at 35 mo | 61 at 60 mo |
| Mel 200 | Mel 200: 200 mg/m2 (single-double) | 21 | |||
| B maintenance18 | B: 1.3 mg/m2 days 1, 15; for 2 y | 36 | |||
| PAD induction | 102 | P: 1.3 mg/m2 days 1, 4, 8, 11; A: 30 mg/m2 day 4; D: 40 mg days 1-4, 8-11, 15-18 (cycles 1-2), days 1-4 (cycles 2-4) | 12 | 66 at 36 mo | 85 at 36 mo |
| Mel 100 | Mel 100: 100 mg/m2 (double) | 33 | |||
| LP consolidation | L: 25 mg days 1-21; P: 50 mg qod; for four 28-d cycles | 40 | |||
| L maintenance19 | L: 25 mg days 1-21 until disease progression | 40 | |||
| BCD induction | 33 | B: 1.3 mg/m2 days 1, 4, 8, 11; C: 300 mg/m2 days 1, 8, 15, 22; D: 40 mg days 1-4, 9-12, 17-20; for four 28-d cycles | 46 ≥ nCR* | ||
| Mel 20020 | Mel 200: 200 mg/m2 (single) | 70 ≥ nCR* | |||
| BTD induction | 236 | B: 1.3 mg/m2 days 1, 4, 8, 11; T: 100-200 mg/d; D: 40 mg days 1, 2, 4, 5, 8, 9, 11, 12; for three 21-d cycles | 19 | 68 at 36 mo | 90 at 36 mo |
| Mel 200 | Mel 200: 200 mg/m2 (double) | 42 | |||
| BTD consolidation21 | B: 1.3 mg/m2 days 1, 8, 15, 22; T: 100 mg/d; D: 40 mg days 1, 2, 8, 9, 15, 16, 22, 23; for two 35-d cycles | 61 | |||
| BTD PACE induction | 303 | B: 1.0 mg/m2 days 1, 4, 8, 11; T: 200 mg days 1-4; D: 40 mg/m2 days 1-4; P: 10 mg/m2 days 1-4; A: 10 mg/m2 days 1-4; C: 400 mg/m2 days 1-4; E: 40 mg/m2 days 1-4; for two ≤ 56-d cycles | 69 at 60 mo | 72 at 60 mo | |
| Mel 200 | Mel 200: 200 mg/m2 (double) | ||||
| BTD PACE consolidation22 | BTD as induction; P: 7.5 mg/m2 days 1-4; A: 7.5 mg/m2 days 1-4; C: 300 mg/m2 days 1-4; E: 30 mg/m2 days 1-4; for two 56-d cycles | 56† | |||
| Drug combinations | |||||
| MPT induction23 | 1685 | M: 0.18 or 0.25 mg/kg days 1-7 or 1-4; P: 2 mg/kg days 1-4; T: 100-200 mg/d; M (0.18 mg) T (100 mg) for six 28-d cycles; M (0.25 mg) T (200 mg) for twelve 42-d cycles | 25 ≥ VGPR | 43 at 24 mo | 50 at 39 mo |
| BMP induction24 | 344 | B: 1.3 mg/m2 days 1, 4, 8, 11, 22, 25, 29, 32 (cycles 1-4), days 1, 8, 22, 29 (cycles 5-9); M: 9 mg/m2 days 1-4; P: 60 mg/m2 days 1-4; for nine 42-d cycles‡ | 30 | 50 at 24 mo | 68 at 36 mo |
| BMPT induction | 254 | B: 1.3 mg/m2 days 1, 8, 15, 22; M: 9 mg/m2 days 1-4; P: 60 mg/m2 days 1-4; T: 50 mg/d; for nine 35-d cycles | 38 | 56 at 36 mo | 89 at 36 mo |
| BT maintenance11 | B: 1.3 mg/m2 every 14 d; T: 50 mg/d for 2 y | 42 | |||
| BLD induction25 | 35 | B: 1.3 mg/m2 days 1, 4, 8, 11; L: 25 mg days 1-14; D: 20 mg days 1, 2, 4, 5, 8, 9, 11, 12 (or days 1, 8, 15); for eight 28-d cycles | 37 | 75 at 18 mo | 97 at 18 mo |
| LD induction12 | 223 | L: 25 mg days 1-21; D: 40 mg days 1-4, 9-12, 17-20; for four 28-d cycles | 5 | 50 at 19 mo | 75 at 24 mo |
| Ld induction12 | 222 | L: 25 mg days 1-21; d: 40 mg days 1, 8, 15, 22; for four 28-d cycles | 4 | 50 at 25 mo | 76 at 24 mo |
| MPL induction | 152 | M: 0.18 mg/kg d 1-4; P: 2 mg/kg d 1-4; L: 10 mg days 1-21; for nine 4-wk cycles | 10 | 50 at 31 mo | 70 at 36 mo |
| L maintenance13 | L: 10 mg days 1-21 until disease progression | 33 ≥ VGPR | |||
| CLd induction26 | 53 | C: 36 mg/m2 days 1, 2, 8, 9, 15, 16; L: 25 mg days 1-21; d: 40-20 mg weekly (cycles 1-4/5-8) for eight 28-d cycles | 79 ≥ nCR* | ||
| Maintenance regimens after stem cell transplantation | |||||
| L maintenance27 | 307 | L: 10-15 mg days 1-21 until disease progression | 29 | 50 at 41 mo | 73 at 48 mo |
| L maintenance28 | 231 | L: 10-15 mg days 1-21 until disease progression | 50 at 46 mo | 88 at 36 mo | |
| Maintenance regimens after drug combinations | |||||
| BT maintenance29 | 91 | B:1.3 mg/m2 twice weekly days 1, 4, 8, 11, every 3 mo; T: 50 mg/d up to 3 y | 44 | 50 at 32 mo | |
| BP maintenance29 | 87 | B: 1.3 mg/m2 twice weekly; days 1, 4, 8, 11, every 3 mo; P: 50 mg qod up to 3 y | 39 | 50 at 24 mo |
| Regimen . | Patients, n . | Schedule . | CR, % . | PFS/EFS/TTP, % . | OS, % . |
|---|---|---|---|---|---|
| Stem cell transplantation | |||||
| BD | 121 | B: 1.3 mg/m2 days 1, 4, 8, 11; D: 40 mg days 1-4 (cycles 1-4), days 9-12 (cycles 1-2); for four 21-d cycles | 6 | 50 at 36 mo | 81 at 36 mo |
| Mel 20017 | Mel 200: 200 mg/m2 (double if < VGPR) | 39 ≥ nCR | |||
| PAD induction | 413 | P: 1.3 mg/m2 days 1, 4, 8, 11; A: 9 mg/m2 days 1-4; D: 40 mg days 1-4, 9-12, 17-20; for three 28-d cycles | 7 | 50 at 35 mo | 61 at 60 mo |
| Mel 200 | Mel 200: 200 mg/m2 (single-double) | 21 | |||
| B maintenance18 | B: 1.3 mg/m2 days 1, 15; for 2 y | 36 | |||
| PAD induction | 102 | P: 1.3 mg/m2 days 1, 4, 8, 11; A: 30 mg/m2 day 4; D: 40 mg days 1-4, 8-11, 15-18 (cycles 1-2), days 1-4 (cycles 2-4) | 12 | 66 at 36 mo | 85 at 36 mo |
| Mel 100 | Mel 100: 100 mg/m2 (double) | 33 | |||
| LP consolidation | L: 25 mg days 1-21; P: 50 mg qod; for four 28-d cycles | 40 | |||
| L maintenance19 | L: 25 mg days 1-21 until disease progression | 40 | |||
| BCD induction | 33 | B: 1.3 mg/m2 days 1, 4, 8, 11; C: 300 mg/m2 days 1, 8, 15, 22; D: 40 mg days 1-4, 9-12, 17-20; for four 28-d cycles | 46 ≥ nCR* | ||
| Mel 20020 | Mel 200: 200 mg/m2 (single) | 70 ≥ nCR* | |||
| BTD induction | 236 | B: 1.3 mg/m2 days 1, 4, 8, 11; T: 100-200 mg/d; D: 40 mg days 1, 2, 4, 5, 8, 9, 11, 12; for three 21-d cycles | 19 | 68 at 36 mo | 90 at 36 mo |
| Mel 200 | Mel 200: 200 mg/m2 (double) | 42 | |||
| BTD consolidation21 | B: 1.3 mg/m2 days 1, 8, 15, 22; T: 100 mg/d; D: 40 mg days 1, 2, 8, 9, 15, 16, 22, 23; for two 35-d cycles | 61 | |||
| BTD PACE induction | 303 | B: 1.0 mg/m2 days 1, 4, 8, 11; T: 200 mg days 1-4; D: 40 mg/m2 days 1-4; P: 10 mg/m2 days 1-4; A: 10 mg/m2 days 1-4; C: 400 mg/m2 days 1-4; E: 40 mg/m2 days 1-4; for two ≤ 56-d cycles | 69 at 60 mo | 72 at 60 mo | |
| Mel 200 | Mel 200: 200 mg/m2 (double) | ||||
| BTD PACE consolidation22 | BTD as induction; P: 7.5 mg/m2 days 1-4; A: 7.5 mg/m2 days 1-4; C: 300 mg/m2 days 1-4; E: 30 mg/m2 days 1-4; for two 56-d cycles | 56† | |||
| Drug combinations | |||||
| MPT induction23 | 1685 | M: 0.18 or 0.25 mg/kg days 1-7 or 1-4; P: 2 mg/kg days 1-4; T: 100-200 mg/d; M (0.18 mg) T (100 mg) for six 28-d cycles; M (0.25 mg) T (200 mg) for twelve 42-d cycles | 25 ≥ VGPR | 43 at 24 mo | 50 at 39 mo |
| BMP induction24 | 344 | B: 1.3 mg/m2 days 1, 4, 8, 11, 22, 25, 29, 32 (cycles 1-4), days 1, 8, 22, 29 (cycles 5-9); M: 9 mg/m2 days 1-4; P: 60 mg/m2 days 1-4; for nine 42-d cycles‡ | 30 | 50 at 24 mo | 68 at 36 mo |
| BMPT induction | 254 | B: 1.3 mg/m2 days 1, 8, 15, 22; M: 9 mg/m2 days 1-4; P: 60 mg/m2 days 1-4; T: 50 mg/d; for nine 35-d cycles | 38 | 56 at 36 mo | 89 at 36 mo |
| BT maintenance11 | B: 1.3 mg/m2 every 14 d; T: 50 mg/d for 2 y | 42 | |||
| BLD induction25 | 35 | B: 1.3 mg/m2 days 1, 4, 8, 11; L: 25 mg days 1-14; D: 20 mg days 1, 2, 4, 5, 8, 9, 11, 12 (or days 1, 8, 15); for eight 28-d cycles | 37 | 75 at 18 mo | 97 at 18 mo |
| LD induction12 | 223 | L: 25 mg days 1-21; D: 40 mg days 1-4, 9-12, 17-20; for four 28-d cycles | 5 | 50 at 19 mo | 75 at 24 mo |
| Ld induction12 | 222 | L: 25 mg days 1-21; d: 40 mg days 1, 8, 15, 22; for four 28-d cycles | 4 | 50 at 25 mo | 76 at 24 mo |
| MPL induction | 152 | M: 0.18 mg/kg d 1-4; P: 2 mg/kg d 1-4; L: 10 mg days 1-21; for nine 4-wk cycles | 10 | 50 at 31 mo | 70 at 36 mo |
| L maintenance13 | L: 10 mg days 1-21 until disease progression | 33 ≥ VGPR | |||
| CLd induction26 | 53 | C: 36 mg/m2 days 1, 2, 8, 9, 15, 16; L: 25 mg days 1-21; d: 40-20 mg weekly (cycles 1-4/5-8) for eight 28-d cycles | 79 ≥ nCR* | ||
| Maintenance regimens after stem cell transplantation | |||||
| L maintenance27 | 307 | L: 10-15 mg days 1-21 until disease progression | 29 | 50 at 41 mo | 73 at 48 mo |
| L maintenance28 | 231 | L: 10-15 mg days 1-21 until disease progression | 50 at 46 mo | 88 at 36 mo | |
| Maintenance regimens after drug combinations | |||||
| BT maintenance29 | 91 | B:1.3 mg/m2 twice weekly days 1, 4, 8, 11, every 3 mo; T: 50 mg/d up to 3 y | 44 | 50 at 32 mo | |
| BP maintenance29 | 87 | B: 1.3 mg/m2 twice weekly; days 1, 4, 8, 11, every 3 mo; P: 50 mg qod up to 3 y | 39 | 50 at 24 mo |
TTP indicates time to progression; VGPR, very good partial response or better; PAD, bortezomib-adriamicyn-dexamethasone (in this schedule, P stands for bortezomib); BCD, bortezomib-cyclophosphamide-dexamethasone; BTD, bortezomib-thalidomide-dexamethasone; BLD, bortezomib-lenalidomide-dexamethasone; BTD-PACE, bortezomib-thalidomide-dexamethasone and cisplatin-doxorubicin-cyclophosphamide-etoposide; LP, lenalidomide-prednisone; qod, every other day; L, lenalidomide; B, bortezomib; BMP, bortezomib-melphalan-prednisone; BMPT, bortezomib-melphalan-prednisone-thalidomide; BT, bortezomib-thalidomide; BP, bortezomib-prednisone; CLd, carfilzomib, lenolidomide, and low-dose dexamethasone; Mel, melphalan; CR, complete response; PFS, progression-free survival; EFS, event-free survival; OS, overall survival; BD, bortezomib-dexamethasone; LD, lenalidomide plus high-dose dexamethasone; Ld, lenalidomide plus low-dose dexamethasone; MPT, melphalan-prednisone-thalidomide; and MPL, melphalan-prednisone-lenalidomide.
In per-protocol population.
Percentage at 2 years.
Alternative BMP schedule11 was B 1.3 mg/m2 days 1, 8, 15, 22; M 9 mg/m2 days 1-4; P 50 mg/m2 days 1-4.