Table 2.
Phase 2 and phase 3 trials evaluating the role of consolidation therapy after ASCT
| References | Age (median), y; no. of patients | Induction therapy | Consolidation therapy | Improvement in depth of response | EFS or PFS* | OS* | Comments | |
|---|---|---|---|---|---|---|---|---|
| Ladetto et al9 | 59 | VAD 4 cycles, single ASCT | VTD | CR: 15%-49% | MRDneg: 68 mo | OS at 8 y | Clear benefit of consolidation therapy and long-term MRD monitoring in MM patients | |
| Ferrero et al10 | N = 39 | MRDneg: 3%-19% | MRDpos: 23 mo (P < .001) | MRDneg: 72%; MRDpos: 42% (P < .041) | ||||
| Cavo et al14 | 57.4; N = 160 | VTD; double ASCT | VTD × 2 | CR: 60.6%; CR/nCR 73.1% | PFS at 3 y: 60%; PFS: median not reached | No difference in OS recorded | No difference in outcome in patients with and without high-risk cytogenetics | |
| 56.8; N = 161 | TD; double ASCT | TD × 2 | CR: 46.6% (P = .012); CR/nCR: 60.9% (P = .020) | PFS at 3 y: 48% (P = .042); PFS: 32 mo | ||||
| Mellqvist et al11 | 59.1; N = 187 | Cyclophosphamide/dexamethasone or high-dose dexamethasone in the majority of patients | 20 Doses of bortezomib given during 21 wk | VGPR: 71%; CR/nCR: 45% | 27 mo | OS at 3 y 80%, no difference between both groups | ||
| Control; 58.7; N = 183 | Single ASCT | None | VGPR: 57% (P < .01); CR/nCR 35 (P = .055) | 20 mo (P = .05) | ||||
| Stadtmauer et al17 | 57; N = 254 | Different regimes | VRD × 4 | n.a. | PFS at 38 mo; 57% | No difference in OS recorded | Largest randomized US transplant trial in MM, showed comparable PFS and OS | |
| N = 257 | Single ASCT | None | PFS at 38 mo; 52% | |||||
| Jackson et al18 | N = 292 | CTD/CTDa | CVD × 4 | From MR/PR to VGPR/CR: 41% | PFS: 30 mo | n.a. | Greater PFS benefit in TE patients | |
| N = 289 | CRD/CRDa | n.a. | PFS: 24 mo | |||||
| Sonneveld et al41 | N = 459 | VCD × 4 plus either VMP or single or double ASCT | RVD × 2 | PFS from R2: 65% | No difference | Benefit seen in patients with revised ISS 3 but not in patients with high-risk cytogenetics | ||
| N = 444 | PFS from R2: 60% | |||||||
| Einsele et al12 | 59 | VCD, VD, VAD, AD, idarubicin/dexamethasone | Four 35-d cycles of bortezomib | Greater than or equal to VGPR: 62% | PFS: 33.6 mo | Similar in both groups | Greater benefit in patients with greater than or equal to VGPR, similar effect in standard- and high-risk patients; 15% of patients discontinued TX because of AE | |
| N = 371 | Single ASCT | VGPR: 48% (P = .003) | PFS: 27.8 mo (P = .0058) | (P = .75) | ||||
| Sezer et al13 | 58.0; N = 51 | Bortezomib based in majority of patients | Four 35-d cycles of bortezomib | sCR/CR: 22%, greater than or equal to VGPR: 80% | 44.9 mo | 40.1 mo | No statistically significant differences | |
| Control: 57.0; N = 53 | Single or double ASCT | None | sCR/CR: 11%; greater than or equal to VGPR: 68% | 21.8 mo | 36.6 mo (P = .098) | |||
AD, doxorubicin-dexamethasone; AE, adverse event; CRD, cyclophosphamide-Revlimid-dexamethasone; CRDa, same as CRD, but 6 cycles; CTD, cyclophosphamide-thalidomide-dexamethasone; CTDa, same as CTD, but 6 cycles; EFS, event-free survival; HR, hazard ratio; ISS, International Staging System; MM, multiple myeloma; MR, minor response; n.a., not available; nCR, near complete remission; R2, second relapse; RVD, Revlimid-Velcade-dexamethasone; TX, treatment; VAD, vincristine-doxorubicin-dexamethasone; VCD, Velcade-cyclophosphamide-dexamethasone; VD, Velcade-dexamethasone; VGPR, very good partial response.
*
Median unless otherwise stated.