Table 1.
Agents studied in maintenance therapy of multiple myeloma.
| Class of agent | Type of agent | Comments | Induction | Consolidation | Efficacy | Reference or ClinicalTrials.gov identifier |
|---|---|---|---|---|---|---|
| Cytokines | Interferon | Tested in phase III trial | Vincristine, adriamycin | Auto transplant with bone marrow stem cells | Increase in PFS; no change in OS | Alexanian et al. [1975] |
| Interferon | Tested in phase III trial (84 patients) | Methylprednisolone (VAMP) or cylophosphamide + VAMP | Melphalan conditioning | No change in PFS (p = 0.09) and OS (p = 0.109) | Cunningham et al. [1998] | |
| Glucocorticoids | Prednisone (prednisone 10 mg versus 50 mg) | Retrospective data, off label (250 patients) | Vincristine, doxorubicin, and dexamethasone with prednisone (VAD-P) or VAD-P plus quinine (VAD-P/Q) | No consolidation | Increase in PFS (14 versus 5 months; p = 0.003); no change in OS (37 versus 26 months; p = 0.05) | Berenson et al. [2002] |
| Prednisone + interferon | Randomized trial (233 patients) | VAD versus VAD plus verapamil or quinine | No consolidation | Increase in PFS median, (19 versus 9 months for IFN; p = 0.008); no change in OS (57 months for IFN/P versus 46 months for IFN; p = 0.36) | Salmon et al. [1998] | |
| Dexamethasone | Randomized trial (307 patients) | Melphalan prednisone versus melphalan dexamethasone | No consolidation | Increase in PFS (2.76 years versus 1.97 years p = 0.000); no change in OS (3.86 years versus 3.65 years p = 0.74). | Shustik et al. [2004] | |
| IMiDs | Thalidomide | Randomized phase III clinical trial (597 patients) | VAD combination chemotherapy of cyclophosphamide, etoposide, vinctistine, adriamycin and dexamethasone | Double ASCT with melphalan | Increase in PFS (p = 0.003) and OS (p = 0.04) | Attal et al. [2006] |
| Randomized phase III clinical trial (668 patients) | VAD versus thalidomide, AD | Double ASCT with melphalan, followed by combination chemotherapy of cyclophosphamide, etoposide, vincristine, adriamycin and dexamethasone | Increase in PFS (56% versus 44%, p = 0.01); no difference in OS | Barlogie et al. [2006] | ||
| Randomized phase III clinical trial (536 patients) | CTD, CVAD, MP | ASCT with melphalan | Increase in PFS (34 months versus 25 months p < 0.001); no difference in OS (60 months versus 73 months p = 0.77) | Lokhorst et al. [2010] | ||
| Meta-analysis | No consolidation | Increase in PFS (23 versus 15 months; p < 0.001); no difference in OS (p = 0.40) | Morgan et al. [2012] | |||
| IMiDs | Lenalidomide | Randomized phase III clinical trial (614 patients) | VAD or bortezomib, dexamethasone | ASCT with melphalan | Increase in PFS (41 months versus 23 months p < 0.001); no difference in OS (80% in lenalidomide group versus 84% in the placebo p = 0.29) | Attal et al. [2012] |
| Randomized phase III (460 patients) | Bortezomib, lenalidomide or thalidomide-based regimens in various combinations | ASCT with melphalan | Increase in PFS (39 months versus 21 months, p < 0.001); OS not reached | McCarthy et al. [2012] | ||
| Proteasome inhibitors | Bortezomib | Randomized phase III clinical trial (386 patients) | VBMCP/VBAD/B versus TD versus VTD | ASCT with melphalan | PFS longer with thalidomide/bortezomib compared with thalidomide alone and with alfa2-IFN (78% versus 63% versus 49%, respectively, at 2 years, p = 0.01); OS was not significantly different in the individual arms | Rosiñol et al. [2012] |
| Randomized phase III clinical trial (627 patients) | VAD versus PAD | ASCT with melphalan | Increase in PFS (13–30 months; HR, 0.45; 95% CI, 0.26–0.78; p = 0.004) and OS (21–54 months; HR, 0.33; 95% CI, 0.16–0.65; p < 0.001), especially in high-risk patients | Sonneveld et al. [2012] |
ASCT, autologous stem cell transplant; CTD, cyclophosphamide, thalidomide, and dexamethasone; MP, melphelan prednisone; VBMCP, vincristine, carmustine, melphalan, cyclophosphamide, prednisone; VBAD/B, vincristine, BCNU, doxorubicin, dexamethasone/bortezomib; VTD, bortezomib, thalidomide and dexamethasone; TD, thalidomide and dexamethasone; CI, confidence interval; PFS, progression-free survival; PAD, bortezomib, doxorubicin and dexamethasone; HR, hazard ratio; OS, overall survival; IFN, interferon; IMiDs, immunomodulating drugs.