Table 4.
Summary of select data from randomized trials for post-ASCT maintenance therapy
| Reference | Patients: total/arms, No. | Median follow-up, mo | Regimen | Dosing schedule | Key efficacy outcomes | Key safety data |
|---|---|---|---|---|---|---|
| Myeloma IX42 | 245 vs 247 | 38 | T vs obs | T 50-100 mg/d continuous | Median PFS: 30 vs 23 mo (HR, 1.42) 3-y OS: 75% vs 80% |
Discontinuation due to AEs: 52.2%; SAE: 8.5% |
| 1098 vs 1333 | NR | Meta-analysis, T vs no T maint, including non-ASCT | Various doses/durations | OS: HR 0.75 7-y OS: 12.3% difference in rate, in favor of T maint |
NR | |
| HOVON-5043,44 | 268 vs 268 | Initial analysis: 52 Follow-up: 129 |
TAd-ASCT-T vs VAd-ASCT-IFN |
T 50 mg/d until PD | Median EFS: 34 vs 22 mo (HR, 0.60); HR 0.62 at follow-up Median PFS: 34 vs 25 mo (HR, 0.67) OS: HR 0.96 OS from relapse 20 vs 31 mo (HR, 1.50) |
T maint: discontinuation due to AEs: 33%; 42% at follow-up (vs 27% IFN) Grade 3-4 PN: 10% |
| NCIC-CTG Myeloma 1045 |
166 vs 166 | 4.1 y | TP vs obs | T 200 mg/d, P 50 mg q2d; up to 4 y | 4-y PFS: 32% vs 14% (HR, 0.55) 4-y OS: 68% vs 60% (HR, 0.77) Median OS postrelapse: 27.7 vs 34.1 mo |
Grade 3/4 thromboembolism: 7.3% vs 0 Grade 3/4 PN: 9.6% vs 1.2% |
| IMWG meta-analysis46 | 1276 vs 1510 | NR | T vs no T maint including non-ASCT | T various doses/durations | PFS: HR 0.65 OS: HR 0.84 |
NR |
| IFM 2005-0225 | 307 vs 307 | 45 | R vs placebo | 10 mg continuous, increase up to 15 mg; until progression | Median PFS: 41 vs 23 mo (HR, 0.50; P < .001) 4-y PFS: 43 vs 22% (P < .001) 4-y OS: 73% vs 75% (P = .7) |
Discontinued for AEs: 27% vs 15%; 2.4 times risk of SPMs with R |
| CALGB 10010426,27 | 231 vs 229 | Initial report: 34 Follow-up: 91 |
R vs placebo post-ASCT | 10 mg continuous, increase up to 15 mg; until progression | Initial: Median PFS/TTP 46 vs 27 mo (HR, 0.48) 3-y OS: 88% vs 80% (HR, 0.62) Follow-up: Median PFS/TTP: 57 vs 29 mo (HR, 0.57; P < .0001) Median OS: 114 vs 84 mo (P = .0004) |
Discontinuation due to AEs: 10% Grade 3/4 neutropenia: 32%/13% vs 12%/3% Heme/solid SPMs: 8%/6% vs 1%/4% |
| RV-MM-20928 | 162 vs 125 (67 vs 68 post-ASCT) | 51.2 | R vs obs post-MPR (n = 132) or ASCT (n = 141) consolidation | 10 mg (21 out of 28 days); until progression | ASCT-R vs ASCT: Median PFS: 54.7 vs 37.4 mo 5-y OS: 78.4% vs 66.6% R maint CR rate improvement: 15.7% to 35.7% R vs no maint, post-MPR/ASCT Median PFS: 41.9 vs 21.6 mo (HR, 0.47) OS: HR 0.64 |
R vs no maint, post-MPR/ASCT Grade 3/4 AEs: Neutropenia 23.3% vs 0% Infections 6.0% vs 1.7% Discontinuation due to AEs: 5.2% vs 0% |
| Phase 3 meta-analysis26 | 605 vs 603 | 79.5 | R vs placebo/obs post-ASCT | R doses varied | Median PFS: 52.8 vs 23.5 mo (HR, 0.48) Median PFS2: 73.3 vs 56.7 mo (HR, 0.72) 7-year OS: 62% vs 50% (HR, 0.75) |
Discontinuation due to AEs: 29.1% vs 12.2% Heme/solid SPMs prior to PD: 5.3%/5.8% vs 0.8%/2.0% |
| Myeloma XI29 | 730 vs 518 | 31 | R vs obs post-ASCT | R 10 mg (21 out of 28 days); until progression | Median PFS: 57 vs 30 mo (HR, 0.48; P < .0001) 3-y OS: 88% vs 80% (HR, 0.69; P = .014) |
Grade 3/4 neutropenia: 28%/5% Discontinuations due to AEs: 28% SPMs: 5.3% vs 3.1% |
|
NCT0109183131 |
60 vs 57 | 41 vs 42.3 | RP vs R alone post-ASCT | RP (R 10 mg, days 1-21, 28-d cycles; P 50 mg, q2d); until progression | Median PFS: 37.6 vs 31.5 mo 4-year OS: 77% vs 75% |
Grade 3/4 AEs: Neutropenia: 8% vs 13% Infections: 8% vs 5% Discontinuations due to AEs: 5% vs 8% |
| GMMG-MM547 | PAd-R → 2 y vs VCd-R → 2 y vs PAd-R → CR vs VCd-R → CR: 125 vs 126 vs 126 vs 125 | 60.1 | R → 2 y vs R CR post-PAd/VCd + ASCT |
R 10-15 mg/d continuous both arms | Median PFS: 43.2 vs 40.9 vs 35.9 vs 35.7 mo 36-mo OS: 83% vs 85% vs 75% vs 77% |
AEs during maintenance (R → 2 y vs R → CR): 77.6% vs 58.2% Grade ≥2 infections (R → 2 y vs R → CR): 52.7% vs 32.3% |
| HOVON-65/GMMG-HD48,49 | 413 vs 414 (270 vs 230 maint) |
Initial analysis: 41 Updated analysis: 96 |
PAd-ASCT-V vs VAd-ASCT-T | V 1.3 mg/m2 IV q2w, up to 2 y T 50 mg/d, up to 2 y |
Initial: Median PFS: 35 vs 28 mo (HR, 0.75) Median PFS from last ASCT: 31 vs 26 mo 5-y OS: 61% vs 55% (HR, 0.81) Updated: Median PFS: 34 vs 28 mo (HR, 0.76) Median OS: 91 vs 82 mo (HR, 0.89) Median OS from relapse: 43 vs 40 mo (HR, 1.02) |
SPMs: 7% in both arms |
| GEM05MENOS6550 |
91 vs 88 vs 92 | 58.6 | VT vs T vs IFN | VT (V 1.3 mg/m2 IV days 1, 4, 8, 11, q3m; T 100 mg/d) vs T (T 100 mg/d) vs IFN (3 MU × 3 per wk) post-ASCT, up to 3 y | Median PFS: 50.6 vs 40.3 vs 32.5 mo 5-year OS: 78% vs 72% vs 70% |
Grade 2-3 PN: 48.8% vs 34.4% vs 1% Discontinuation due to toxicity: 21.9% vs 39.7% vs 20% |
| Tourmaline-MM351 | 395 vs 261 | 31 | Ixazomib vs placebo post-ASCT | Ixazomib 3-4 mg, days 1, 8, 15, 28-d cycles; up to 2 y | Median PFS: 26.5 vs 21.3 mo (HR, 0.72) |
Grade ≥3 AEs: 42% vs 26% Grade ≥3 infections/infestations: 15% vs 8% Grade ≥3 GI disorders: 6% vs 1% Discontinuation due to AEs: 7% vs 5% |
AE, adverse event; CR, complete response; EFS, event-free survival; GI, gastrointestinal; heme, hematologic; IMWG, International Myeloma Working Group; IFN, interferon; IV, intravenous; MPR, melphalan, prednisone, lenalidomide; MU, million units; P, prednisone; PAd, bortezomib, doxorubicin, dexamethasone; PD, progressive disease; PFS2, progression-free survival from start of treatment to progression on next line of treatment; PN, peripheral neuropathy; q2d every other day; q2w, every 2 weeks; q3m, every 3 months; R, lenalidomide; RP, lenalidomide, prednisone; SAE, serious adverse event; SPM, second primary malignancy; T, thalidomide; TAd, thalidomide, doxorubicin, dexamethasone; TP, thalidomide, prednisone; TTP, time to progression; V, bortezomib; VAd, vincristine, doxorubicin, dexamethasone; VT, bortezomib, thalidomide.