Summary of the efficacy and safety results of maintenance in MM after HDT-ASCT in transplant-eligible patients
| Reference . | n . | Trial and follow-up . | Maintenance . | Response upgrade . | PFS/EFS . | Survival . | Tolerance and additional data . |
|---|---|---|---|---|---|---|---|
| 14 | 614 | IFM 2005/02 45 mo | A: Len, 10-15 mg/d × 21 d until PD*; B: placebo | A: CR 29%; B: CR 27% | First data: A, PFS 41 mo (P < .001); B, PFS 23 mo; update (64 mo of follow-up): A, 5-y PFS2 ∼60% (P < .07); B, 5-y PFS2 ∼53% | 30 mo: 3-y A 80% vs B 88% (P = .2); 45 mo: 4-y A 73% vs 75% (P = .7); 67 mo: A 82 mo vs B 80 mo (P = .8) | A: discontinuations for DRAEs, 21%; maintenance improved the rate of CR and VGPR (P = .009); PFS maintenance benefit in 13 q deletion t(4-14) or 17 p deletion cases; reduced survival after first progression (29 vs 48 mo); 2.4-fold greater risk of SPMs with Len maintenance |
| 29 | 460 | CALGB 00104 34 mo | Post-ASCT ≥ stable disease; A: Len, 5-15 mg/d × 21 d until PD; B: placebo | NA | First data: A, 3-y PFS 66% (P < .001); B, 3-y PFS 39% | 34 mo: A 3-y 88% vs B 80% (P = .03); 48 mo: A NR vs 73 mo. (P = .008) | A: discontinuations for DRAEs 12%; OS including placebo patients crossing over within 6 mo of randomization on the Len arm (P = .003); threefold greater risk of SPMs with Len maintenance; better prognosis for patients treated with Len in induction |
| 22 | 402 | NCT00551928 51 mo | 2 × 2 factorial randomized trial; A: Len (10 mg/d × 21 d until PD); B: observation | A: CR 34%; B: CR 29% | A: median PFS: 42 mo (P < .001); B: 2-y PFS: 21.6 mo | 36 mo OS A 88% vs B 79% (P = NS) | DRAEs similar in the PredLen and Len arms (infections 3% vs 3%) |
| 34 | 828 | Myeloma XI 27 mo | A: Len (10 mg/d × 21 d until PD); B: observation | NA | A: median PFS 50 mo (P < .0001); B: 2-y PFS 28 mo | NA | Outcome of high-risk patients better in the Len arm; no increase in DNA instability at the mutational or structural level |
| 23 | 223 | Italian study 52 mo | A: Len (10 mg/d × 21 d) plus prednisone 50 mg every other day until DP; B: Len (10 mg/d × 21 d until PD) | A: CR 30%; B: CR 30% | A: median PFS 37.5 mo (P = NS); B: median PFS: 28.5 mo | 36 mo OS A 83% vs B 88% (P = NS) | The frequency of mild cutaneous and hematological adverse events was slightly inferior in the Len plus prednisone arm |
| 32, 36 | 827 | HOVON-65 67 mo | A: VAD-1/2ASCT- Thal 50 mg/d × 2y; B: PAD-1/2ASCT- Bor 1.3 mg/m2 IV/2 wk | A: Thal CR 11%; B: Bor CR 12% | PAD-ASCT-Bor: HR = 0.76, P = .001 | PAD-ASCT-Bor: HR = 0.78, P = .02 | 5-y OS for PAD-Btz (vs VAD-Thal plus tandem ASCT was superior (P = .004) |
| 7, 35 | 266 | GEM05 <65 35 mo | A: Thal 100 mg/d + Bor (1 cycle/ 3 mo) × 3 y; B: Thal 100 mg/d × 3 y; C: α-interferon × 3 y | A: CR 19%; B: CR 15%; C: CR 17% | A: PFS longer compared with B or C (P = .0009) | OS similar in the 3 arms | Thal discontinuations: A 16%, B 30% |
| Nooka et al46 | 45 | RVD high-risk patients 26 mo | RVD: Len 10 mg 21/28, Bor 1.3 mg/m2 subcutaneous/IV weekly, Dexa 40 mg weekly for up to 3 y | 51% sCR | 32 mo | 93% at 3 y | No grade 3-4 PN |
| 11 | 65 | Ixa after IRd of induction 14 mo | Ixa: 4 mg weekly | 37% VGPR | 88% at 1 y | 94% at 1 y | No grade 3-4 side effects |
| Reference . | n . | Trial and follow-up . | Maintenance . | Response upgrade . | PFS/EFS . | Survival . | Tolerance and additional data . |
|---|---|---|---|---|---|---|---|
| 14 | 614 | IFM 2005/02 45 mo | A: Len, 10-15 mg/d × 21 d until PD*; B: placebo | A: CR 29%; B: CR 27% | First data: A, PFS 41 mo (P < .001); B, PFS 23 mo; update (64 mo of follow-up): A, 5-y PFS2 ∼60% (P < .07); B, 5-y PFS2 ∼53% | 30 mo: 3-y A 80% vs B 88% (P = .2); 45 mo: 4-y A 73% vs 75% (P = .7); 67 mo: A 82 mo vs B 80 mo (P = .8) | A: discontinuations for DRAEs, 21%; maintenance improved the rate of CR and VGPR (P = .009); PFS maintenance benefit in 13 q deletion t(4-14) or 17 p deletion cases; reduced survival after first progression (29 vs 48 mo); 2.4-fold greater risk of SPMs with Len maintenance |
| 29 | 460 | CALGB 00104 34 mo | Post-ASCT ≥ stable disease; A: Len, 5-15 mg/d × 21 d until PD; B: placebo | NA | First data: A, 3-y PFS 66% (P < .001); B, 3-y PFS 39% | 34 mo: A 3-y 88% vs B 80% (P = .03); 48 mo: A NR vs 73 mo. (P = .008) | A: discontinuations for DRAEs 12%; OS including placebo patients crossing over within 6 mo of randomization on the Len arm (P = .003); threefold greater risk of SPMs with Len maintenance; better prognosis for patients treated with Len in induction |
| 22 | 402 | NCT00551928 51 mo | 2 × 2 factorial randomized trial; A: Len (10 mg/d × 21 d until PD); B: observation | A: CR 34%; B: CR 29% | A: median PFS: 42 mo (P < .001); B: 2-y PFS: 21.6 mo | 36 mo OS A 88% vs B 79% (P = NS) | DRAEs similar in the PredLen and Len arms (infections 3% vs 3%) |
| 34 | 828 | Myeloma XI 27 mo | A: Len (10 mg/d × 21 d until PD); B: observation | NA | A: median PFS 50 mo (P < .0001); B: 2-y PFS 28 mo | NA | Outcome of high-risk patients better in the Len arm; no increase in DNA instability at the mutational or structural level |
| 23 | 223 | Italian study 52 mo | A: Len (10 mg/d × 21 d) plus prednisone 50 mg every other day until DP; B: Len (10 mg/d × 21 d until PD) | A: CR 30%; B: CR 30% | A: median PFS 37.5 mo (P = NS); B: median PFS: 28.5 mo | 36 mo OS A 83% vs B 88% (P = NS) | The frequency of mild cutaneous and hematological adverse events was slightly inferior in the Len plus prednisone arm |
| 32, 36 | 827 | HOVON-65 67 mo | A: VAD-1/2ASCT- Thal 50 mg/d × 2y; B: PAD-1/2ASCT- Bor 1.3 mg/m2 IV/2 wk | A: Thal CR 11%; B: Bor CR 12% | PAD-ASCT-Bor: HR = 0.76, P = .001 | PAD-ASCT-Bor: HR = 0.78, P = .02 | 5-y OS for PAD-Btz (vs VAD-Thal plus tandem ASCT was superior (P = .004) |
| 7, 35 | 266 | GEM05 <65 35 mo | A: Thal 100 mg/d + Bor (1 cycle/ 3 mo) × 3 y; B: Thal 100 mg/d × 3 y; C: α-interferon × 3 y | A: CR 19%; B: CR 15%; C: CR 17% | A: PFS longer compared with B or C (P = .0009) | OS similar in the 3 arms | Thal discontinuations: A 16%, B 30% |
| Nooka et al46 | 45 | RVD high-risk patients 26 mo | RVD: Len 10 mg 21/28, Bor 1.3 mg/m2 subcutaneous/IV weekly, Dexa 40 mg weekly for up to 3 y | 51% sCR | 32 mo | 93% at 3 y | No grade 3-4 PN |
| 11 | 65 | Ixa after IRd of induction 14 mo | Ixa: 4 mg weekly | 37% VGPR | 88% at 1 y | 94% at 1 y | No grade 3-4 side effects |
Bor, bortezomib; Dexa, dexamethasone; DRAEs, drug-related adverse events; EFS, event-free survival; HR, hazard ratio; IRd, ixazomib, lenalidomide, and dexamethasone; Ixa, ixazomib; Len, lenalidomide; NA, not available; NR, not reached; NS, not significant; PAD, bortezomib, adriamycin and dexamethasone; PD, progressive disease; RVD, lenalidomide, bortezomib, and dexamethasone; sCR: stringent complete response; SPMs, secondary primary malignancies; Thal, thalidomide.
Maintenance stopped after a median of 24 mo.