Table 1.
Details of induction regimens of included RCTs
| Study | Group | Accrual period | Induction regimens; drugs (day administered) × no. of cycles (duration, days) |
|---|---|---|---|
| Rajkumar et al22 | TD Dex |
June 2002–April 2003 | Tha: 200 mg (1–28) × 4 (28), Dex: 40 mg (1–4, 9–12, 17–20) × 4 (28) Dex: 40 mg (1–4, 9–12, 17–20) × 4 (28) |
| Sonneveld et al24 | VAD PAD |
May 2005–May 2008 | Vin: 0.4 mg (1–4) × 3 (28), dox: 9 mg/m2 (1–4) × 3 (28), Dex: 40 mg (1–4, 9–12, 17–20) × 3 (28) Bor: 1.3 mg/m2 (1, 4, 8, 11) × 3 (28), dox: 9 mg/m2 (1–4) × 3 (28), Dex: 40 mg (1, 4, 9–12, 17–20) × 3 (28) |
| Moreau et al25 | VD VTD |
March 2008–January 2009 | Bor: 1.3 mg/m2 (1, 4, 8, 11) × 4 (21), Dex: 40 mg (1–4 [all cycles], 9–12 [cycles 1 and 2]) × 4 (21) Bor: 1 mg/m2 (1, 4, 8, 11) × 4 (21), tha: 100 mg (1–21) × 4 (21), Dex: 40 mg (1–4 [all cycles], 9–12 [cycles 1 and 2]) × 4 (21) |
| Rosiñol et al26 | VTD TD VBMCP/VBAD/B |
April 6, 2006–August 5, 2009 | Bor: 1.3 mg/m2 (1, 4, 8, 11) × 6 (28), tha: 50 mg (1–14) + 100 mg (15–28) × 1 (28) then 200 mg (1–28) × 5 (28), Dex: 40 mg (1–4, 9–12) × 6 (28) Tha: 50 mg (1–14) + 100 mg (15–28) × 1 (28) then 200 mg (1–28) × 5 (28), Dex: 40 mg (1–4, 9–12) × 6 (28) VBMCP consisted of BCNU: 0.5 mg/kg (1), vin: 0.03 mg/kg (1; upper limit 2 mg), mel: 0.25 mg/kg (1–4), pre: 1 mg/kg (1–4) + 0.5 mg/kg (5–8) + 0.25 mg/kg (9–12). VBAD consisted of vin: 1 mg (1), BCNU: 30 mg/m2 (1), dox: 40 mg/m2 (1), Dex: 40 mg (1–4, 9–12, 17–20) (alternate VBMCP and VBAD; total four cycles × 35 days), bor: 1.3 mg/m2 (1, 4, 8, 11) × 2 (21) |
| Lokhorst et al14 | TAD VAD |
November 27, 2001–May 31, 2005 | Tha: 200–400 mg (1–28) × 3 (28), dox: 9 mg/m2 (1–4) × 3 (28) then Dex: 40 mg (1–4, 9–12, 17–20) × 3 (28) Vin: 0.4 mg (1–4) × 3 (28), dox: 9 mg/m2 (1–4) × 3 (28), Dex: 40 mg (1–4, 9–12, 17–20) × 3 (28) |
| Moreau et al27 | VTD VDC |
November 2013–March 2015 | Bor: 1.3 mg/m2 (1, 4, 8, 11) × 4 (21), Dex: 40 mg (1–4, 9–12) × 4 (21), tha: 100 mg (1–21) × 4 (21) Bor: 1.3 mg/m2 (1, 4, 8, 11) × 4 (21), Dex: 40 mg (1–4, 9–12) × 4 (21), cyc: 500 mg/m2 (1, 8, 15) × 4 (21) |
| Cavo et al28 | TD VAD |
January 2002–January 2004 | Tha: 100 mg (1–14) then 200 mg × 4 (30), Dex: 40 mg (1–4, 9–12, 17–20; odd cycles) + 40 mg (1–4; even cycles) × 4 (30) Vin: 0.4 mg (1–4) × 4 (30), dox: 9 mg/m2 (1–4) × 4 (30), Dex: 40 mg (1–4, 9–12, 17–20; odd cycles) + 40 mg (1–4; even cycles) × 4 (30) |
| Ludwig et al21 | VTD VTDC |
October 2007–September 2009 | Bor: 1.3 mg/m2 (1, 4, 8, 11) × 4 (21), Dex: 40 mg (1–4, 9–12) × 4 (21), tha: 100 mg (1–21) × 4 (21) Bor: 1.3 mg/m2 (1, 4, 8, 11) × 4 (21), Dex: 40 mg (1–4, 9–12) × 4 (21), tha: 100 mg (1–21) × 4 (21), cyc: 400 mg/m2 (1, 8) × 4 (21) |
| Harousseau et al29 | VD VAD |
August 9, 2005–January 18, 2008 | Bor: 1.3 mg/m2 (1, 4, 8, 11) × 4 (21), Dex: 40 mg (1–4 [all cycles], 9–12 [cycles 1 and 2]) × 4 (21) Vin: 0.4 mg (1–4) × 4 (28), dox: 9 mg/m2 (1–4) × 4 (28), Dex: 40 mg (1–4 [all cycles], 9–12, 17–20 [cycles 1 and 2]) × 4 (28) |
| Mai et al30 | VDC PAD |
July 2010–October 2012 | Bor: 1.3 mg/m2 (1, 4, 8, 11) × 3 (21), Dex: 40 mg (1–2, 4–5, 8–9, 11–12) × 3 (21), cyc: 900 mg/m2 (1) × 3 (21) Bor: 1.3 mg/m2 (1, 4, 8, 11) × 3 (28), dox: 9 mg/m2 (1–4) × 3 (28), Dex: 40 mg (1–4, 9–12, 17–20) × 3 (28) |
| Cavo et al12 | VTD TD |
May 2006–April 2008 | Bor: 1.3 mg/m2 (1, 4, 8, 11) × 3 (21), tha: (100 mg [1–14) + 200 mg [15–21]) × 3 (21), Dex: 40 mg (1, 2, 4, 5, 8, 9, 11, 12) × 3 (21) Tha: (100 mg [1–14] + 200 mg [15–21]) × 3 (21), Dex: 40 mg (1–4, 9–12) × 3 (21) |
| Mellqvist et al31 | VAD Cy-Dex |
November 2001–October 2003 | Vin: 1.6 mg/m2 (1–4) × 3 (28), dox: 36 mg/m2 (1–4) × 3 (28), Dex: 40 mg (1–4, 9–12, 17–20) × 3 (28) Cyc: 1000 mg/m2 (1) × 2 (21), Dex: 40 mg (1–4, 9–12) × 2 (21) |
| Kumar et al32 | VDCR VDR VDC VCD-mod |
June 2008–September 2009 | Bor: 1.3 mg/m2 (1, 4, 8, 11) × 8 (21), Dex: 40 mg (1, 8, 15) × 8 (21), cyc: 500 mg/m2 (1, 8) × 8 (21), len: 15 mg (1–14) × 8 (21) Bor: 1.3 mg/m2 (1, 4, 8, 11) × 8 (21), Dex: 40 mg (1, 8, 15) × 8 (21), len: 25 mg (1–14) × 8 (21) Bor: 1.3 mg/m2 (1, 4, 8, 11) × 8 (21), Dex: 40 mg (1, 8, 15) × 8 (21), cyc: 500 mg/m2 (1, 8) × 8 (21) Bor: 1.3 mg/m2 (1, 4, 8, 11) × 8 (21), Dex: 40 mg (1, 8, 15) × 8 (21), cyc: 500 mg/m2 (1, 8, 15) × 8 (21) |
| Kumar et al33 | TD RD |
April 2009–September 2014 | Tha: 200 mg (1–28) × 4 (28), Dex: 40 mg (1–4, 9–12) × 4 (28) Len: 25 mg (1–21) × 4 (28), Dex: 40 mg (1–4, 9–12) × 4 (28) |
Abbreviations: bor, bortezomib; BCNU, bischloroethylnitrosourea; cyc, cyclophosphamide; Cy-Dex, cyclophosphamide plus dexamethasone; Dex, dexamethasone; dox, doxorubicin; len, lenalidomide; mel, melphalan; PAD, bortezomib plus doxorubicin plus dexamethasone; pre, prednisone; RCTs, randomized controlled trials; RD, lenalidomide plus dexamethasone; TAD, thalidomide plus doxorubicin plus dexamethasone; TD, thalidomide plus dexamethasone; tha, thalidomide; VAD, vincristine plus doxorubicin plus dexamethasone; VBMCP-VBAD-B, BCNU plus vincristine plus melphalan plus prednisone plus dexamethasone plus bortezomib; VD, bortezomib plus dexamethasone; VDCR, bortezomib plus dexamethasone plus cyclophosphamide plus lenalidomide; VDR, bortezomib plus dexamethasone plus lenalidomide; vin, vincristine; VTD, bortezomib plus thalidomide plus dexamethasone; VTDC, bortezomib plus thalidomide plus dexamethasone plus cyclophosphamide.