Table 2.
| Study author | Study type (phase) | Number of patients and groups | Regimen | Dosage | Usage | Cycles received | ORR (%) | Survival | Common toxicity | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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|
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| Scr | CR/nCR | VGPR | PR | PFS | OS | ||||||||
| Jagannath et al55,59 | II | 49 | B + BD | B—1.3 mg/m2 on days 1, 4, 8 and 11. D—40 mg/m2 if no PR ≤ 2 OR CR ≤ 4 weeks on B |
First-line | 6 | 3 | 9 | 14 | Reversible sensory neuropathy | |||
| Wang et al99 | Retrospective | 38 | BTD ± BMSCT | B—1.3 mg/m2 on days 1, 4, 8 and 11 T—100 mg/day increased to a maximum of 200 mg/day D—20 mg/2 on 1, 9 and 17 for 4 days |
First-line | 3-four week cycles | 16 | PR-71 ≥ PR-87 | Fatigue, GI AE’s, rash, edema, ↓ blood counts, neuropathy | ||||
| Popat et al47 | I/II | 41 21 (BAD1) 20 (BAD2) |
BAD (1) vs. BAD (2) | P—1.3 mg/m2 in (1) vs.1.0 mg/m2 in (2) on days 1, 4, 8 and 11 A—0–9 mg/m2 on days 1–4 D—40 mg/2 on days 1–4, 8–11 and 15–18 |
Front-line Induction | 4 | (1) 29 (2) 16 |
(1) 33 (2) 26 |
(1) 33 (2) 47 |
(1) 29 months (2) 24 months |
2 years (1) 95% (2) 73% |
Liver, GI, psychiatric, fatigue, neuropathy, skin, ↓ platlets | |
| Richardson et al63 | II | 64 | B | B—1.3 mg/m2 on days 1, 4, 8, 11 | First-line | 8 | 9 | 8 | 31 | 17 months | 2.5 years 79% |
Sensory neuropathy, GI AE’s, fatigue, rash, ↓ blood counts | |
| Vista trial56 | III | 682 337(BMP) 331(MP) |
BMP (a) vs. MP (b) | B—1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29 and 32 M—9 mg/m2 6 weeks P—60 mg/m2 on days 1–4 |
First-line transplant ineligible | 9 | 33 (a) 4 (b) |
8 (a) 4 (b) |
33 (a) 31 (b) |
3.7 years (a) not 50% (b) 50% |
Peripheral neuropathy, ↓ blood counts, GI AE’s, pneumonia | ||
| IFM 2005-0153 | III | 482 VAD (A1-121) VAD + DCEP (A2-121) BD (B1-121) BD + DCEP (B2-119) |
A1 + A2 – (C-218) vs. B1 + B2 – (D-223) | Vin—0.4 mg/d four 4 week cycles Dox—9 mg/m2/d, on days 1–4. Dex—40 mg on days 1–4 B—1.3 mg/m2 four 3 weeks cycle on days 1, 4, 8 and 11 D—40 mg on days 1 to 4 all cycles and 9–12 (cycles 1 and 2) DCEP*– On days 1–4 |
Induction prior to auto-PBSCT | 6.4 (C) 14.8 (D) |
15.4 (C) 37.7 (D) |
(C) 29.7 months (D) 36 months |
2.10 years (C) not 50% (D) not 50% |
PN, Fatigue, ↓ blood counts, hemorrhages, infections, GI AE’s, Herpes zoster infection, Rash, | |||
| Mateos et al57,65 | Pilot and randomized trial | 260 260— Induction** 130—BMP (A) 130—BTP (B) 178— Maintenance# 87—BP (C) 91—BR (D) |
(A) vs.(B) and (C) vs.(D) | B—1.3 mg/m2 2x/week on days 1, 4, 8, 11, 22, 25, 29 and 32 (for one-6 week cycle) and same dosage for days 1,8, 15 and 22 (for five-5 week cycles) **M—9 mg/m2 on days 1–4 P—60 mg/m2 on days 1–4 T—100 mg/day B—1.3 mg/m2 on days 1, 4, 8 and 11 every 3 month P—50 mg every 48 hrs #R—50 mg/day |
Induction and maintenance | **(A) and (B) One, 6-week cycle each and five, 5–week cycles #≥ 3 yrs | (A) CR-20; nCR-12. (B) CR-28 nCR-8 |
(A)-48 (B)-45 |
At first randomization 31 months for all. (FU 32 months) At second randomization 32 months for (C) and 24 months for (D) (FU 22 months) |
At 3 years was 70% for all groups | ↓ blood counts, GI AE’s, Peripheral neuropathy, DVT/thromboembolism, cardiac events | ||
| Richardson et al58 | I/II | 66 | BRD | Planned eight-3 week cycles of-B—1.3 mg/m2 on days 1, 4, 8 and 11 R—25 mg on days 1–14 D—20 mg (cycles 1–4) and then 10 mg (for cycles 5–8) |
10-median number of cycles per drug including maintenance | Phase I— CR-29 nCR-11 Phase II— CR-37 nCR-20 |
Phase I—27 Phase II—17 |
Phase I—33 Phase II—26 (100% atleast PR) |
Fatigue, GI AE’s, NS AE’s, ↓ blood counts, ↓ K+, PE | ||||
| Cavo et al54 | III | 474 236—(A) 238—(B) |
BTD vs TD ± Double BMSCT | Induction B—1.3 mg/m2 on days 1, 4, 8 and 11 T—100 mg/day from 1–14 days and 200 mg/day thereafter D—in BTD (40 mg on days 1, 2, 4, 5, 8, 9 and 11) and in TD (40 mg on days 1–4 and 9–12). Consolidation B—1.3 mg/m2 on days 1, 8, 15 and 22 T—100 mg/day D—40 mg on days 1, 2, 8, 9, 15, 16, 22 and 23 for BTD and same dose on days 1–4 and 20–23 for TD Maintenance D—40 mg on days 1–4, every 28 days |
Induction and Consolidation Maintenance |
Three-21 days induction cycle of each Two-35 days consolidation cycles of each |
BTD CR-58 ≥nCR-71 TD CR-41 ≥nCR-54 |
BTD ≥VGPR −89 TD ≥VGPR −74% |
BTD ≥PR-96 TD ≥PR-89 |
At 3 years BTD—68% TD—56% |
At 3 year BTD—86% TD—84% |
Constipation, neuropathy, rash, fever, infection, oedema, GI AE’s, hematological AE’s | |
| Palumbo et al90 | III | 511 BMPT (254) + BT* (A) (maintenance)* BMP (257) (B) | (A) vs.(B) No maintenance for (B) | B—1.3 mg/m2 on days 1, 8, 15 and 22 M—9 mg/m2 on days 1–4 P—60 mg/m2 on days 1–4 T—50 mg/day continuously |
Induction and maintenance for (A) only | 9-five week cycles | (A) 38 (B) 24 |
(A) 21 (B) 26 |
(A) 30 (B) 31 |
At 3 years 56% (A) 41% (B) |
At 3 years 89% (A) 87% (B) |
↓ blood counts, cardiac AE’s, NS AE’s, infections, vascular events, fatigue, rash | |
| Ghosh et al82 | II | 27 | BT | B—1.3 mg/m2 on days 1, 4, 8 and 11 every 21 days T—150 mg/day |
Frontline | 8 weeks | CR-10 nCR-13.3 |
6.6 | 43.3 | 16.8 months | At 3 years 74% | GI AE’s, NS AE’s, infection, fatigue, rash, ↓ blood counts | |
| Reeder et al75 | II | 28 | CBD ± BMSCT | C—300 mg/m2 on days 1, 8, 15 and 22 B—1.3 mg/m2 on days 1, 4, 8 and 11 D—40 mg on days 1–4,9–12, 17–20 and 28 |
Induction | 4-four week cycles | 39 | ≥VGPR-61 | ≥PR-88 | ↓ blood counts, hyperglycemia, diarrhea, ↓ K+, neuropathy, ↓ blood counts, infections, fatigue, GI AE’s, PN | |||
| Moreau et al85 | III | 199 100 btD (A) 99 BD (B) |
(A) vs.(B) ± BMSCT | B—1.3 mg/m2 on days 1, 4, 8 and 11 D—40 mg on days 1–4 (all cycle) and 9–12 (on cycle 1 and 2) b—1.0 mg/m2 on days 1, 4, 8 and 11 t—100 mg/day |
Induction | 4-three week cycles | ≥nCR (A)-31 (B)-22 CR (A)-13 (B)-12 |
≥VGPR (A)-49 (B)-36 |
PR (A)-88 (B)-81 |
A—30 months B—26 months |
No difference | ||
| Lee et al100 | II | 31 | BAD ± BMSCT and T | B—1.3 mg/m2 on days 1, 4, 8 and 11 A—9 mg/m2 on days 1–4 D—40 mg on days 1–4 and 8–11 T-100–200 mg/day post-transplant (Maintenance) |
Induction | 2-three week cycles | Induction CR-19.3 Maintenance CR-70 |
Induction −16.1 Maintenance −23.3 |
Induction −45.2 Maintenance −6.7 |
At 5 years 23.5% | At 5 years 71.1% | ↓ blood counts, nausea, vomiting, PN, hepatotoxicity | |
| Roussel et al69 | II | 54 | B-HDM | B—1.0 mg/m2 on days −6, −3, +1 and +4 HDM—200 mg/m2 on days −2. |
Conditioning | Pre-transplant only | 32 | 38 | 24 | At 2 years 96% | Mucositis, Skin rash, GI AE’s, PN | ||
| Kim et al73 | II | Total 71; 65 evaluated | VAD + *BTD + BMSCT + B# | Vin—0.4 mg/day continuous on A—same as Vincristine days 1–4 D—40 mg on days 1–4 and 9–12 B—1.3 mg/m2 on days 1, 4, 8 and 11 T—100 mg/day #1.3 mg/m2 weekly |
*Induction #Consolidation |
VAD and BTD 2-three week cycles each #4 cycles on 4 of every 6 week |
*nCR-27 CR-17 After # ≥nCR-75 CR-72 |
*≥VGPR-54 After #≥VGPR-81 |
*≥PR-97 After #≥PR-94 |
29.4 months | Not reached at 29.4 months | ↓ blood counts, peripheral neuropathy, DM, infection, thrombosis | |
| Gasparetto et al68 | II | 44 24 (BMP only) 20 (BMSCT) |
BMP (only)* ± BMSCT # | B—1.3 mg/m2 on days 1, 4, 8 and 11 M—6 mg/m2 on days 1–7 P—6 mg/m2 on days 1–7 |
Frontline or as Induction | 6-four week cycles | *8 #10 |
*CR-17 #CR-20 |
*17 #65 |
*50 #5 |
*19.8 months #27.9 months |
At 1 year *82% #95% |
PN, GI AE’s infection, ↓ blood counts, DVT, orthostatic hypotension |
| PETHEMA64 | II | 40 | BD ± BMSCT* | B—1.3 mg/m2 on days 1, 4, 8 and 11 (cycles 1,3 and 5) D—40 mg on days 1 to 4, 9 to 12 and 17 to 20 (cycles 2, 4 and 6) |
Induction | 3-four week cycles | 12.5* 33 |
7.5* 22 |
40 * 33 | Thrombocytopenia, fatigue neutropenia, PN, rash, | |||
| PETHEMA84 | III | 266 TB—90 (A) T—89 (B) α2-INF— 87 (C) |
Maintenance | For 3 years | Post SCT | ||||||||
| A vs.B vs. C Post-SCT |
T—100 mg/day B—1.3 mg/m2 on days 1, 4, 8 and 11 every 3 months α2-INF—3MU thrice/week |
CR-51 | VGPR-23 | PR-24 | At 2 years (A) 78% (B) 63% (C) 49% |
No significant difference between the three arms | 266 TB—90 (A) T—89 (B) α2-INF —87 (C) |
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| Improved CR after maintenance by (A) 21 (B) 11 (C) 19 | |||||||||||||
| Sahebi et al98 | II | 45 | BD then TD and then T Post-ASCT | B—1.3 mg/m2 on days 1,8 and 28 D—40 mg on days 1 through 4 T—50 mg to a maximum of 200 mg/day for 28 days |
Maintenance | Six-28 days cycle of BD then TD and then T until progression or toxicity | At 6 months CR post B-52.5 At 1 year CR post T-50 |
At 6 months B-17.5 At 1 year T-5 |
At 6 months B-20 At 1 year T-7.5 |
At 1 year was 88% | At 1 year was 95% | PN, ↓ blood counts, fatigue, GI AE’s, hyperglycemia, insomnia | |
| Landau et al72 | II | 42 | BLDD then either TD or BTD depending on response |
BLDD– B-1.3 mg/m2 on days 1, 4, 8 and 11 LD-30 mg/m2 on day 4D-20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 TD—If ≥ PR T-50 mg to 200 mg max on days 1–28 D-40 mg on days 1–4, 9–12 and 17–20 BTD—If SD or PD B-1.3 mg/m2 on days 1, 4, 8 and 11 T-50 mg to 200 mg max on days 1–28 D-20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 and 40 mg on days 17–20 |
Induction | Three-21 days cycle of BLDD, followed by either two-28 days of TD or two-28 days cycles of BTD | ncr/CR-43 | ≥VGPR-60 | ≥PR-60 | At 1 year 88% At 2 years 83% OS was better if ≥ PR post BLDD with either TD or BTD | Fatigue, rash GI AE’s, neuropathy, ↓ blood counts, thrombosis, | ||
| Evolution Study81,88 | I and II | 140 BDCR(48)-(A) BDR(42)-(B) BDC(33)-(C) BDC-Mod(17)-(D) |
A vs.B vs. C vs. D | B—1.3 mg/m2 on days 1, 4, 8 and 11. D—40 mg/m2 on days 1, 8 and 15. C—500 mg/m2 on days 1 and 8 only for (D) on day 15 as well R—Days 1–4 for (A) 15 mg and (B) 25 mg |
Frontline | 12 | (A) 15 (B) 17 (C) 9 (D) 29 |
(A) 25 (B) 24 (C) 22 (D) 47 |
(A) 58 (B) 51 (C) 41 (D) 53 |
At 1 year (A) 86% (B) 83% (C) 93% (D) 100% |
Neutropenia, peripheral neuropathy, GI AE’s | ||
| HOVON74 | III | 827 414 (VAD + HDM + T) −(A) 413(BAD + HDM +B) − (B) |
(A) vs.(B) | Induction Vin— 0.4 mg/day continuous on A—same as Vincristine days 1–4 D—40 mg on days 1–4 and 9–12 B—1.3 mg/m2 on days 1, 4, 8 and 11 A—9 mg/m2 on days 1–4 D—40 mg on days 1–4, 9–12 and 17–20 Maintenance B—1.3 mg/m2, two-weekly T—50 mg/day |
(A) and (B) have components for Induction, pre-transplant and maintenance | 3 cycles of VAD or BAD 1 or 2 doses of HDM 2 years of maintenance (B or T) | (A) 38 (B) 50 |
(A) 61 (B) 75 |
(A) 87 (B) 92 |
At 3 years (A) 42 (B) 48 |
At 3 years (A) 71 (B) 78 |
Infection, GI AE’s, PN | |