Table 3.
Summary of data from key phase 3 studies/meta-analyses reporting comparative data on post-ASCT maintenance.
| Study | Treatment (maintenance dose/duration) | N | Follow-up | DoT | Key efficacy outcomes | Key safety and tolerability data |
|---|---|---|---|---|---|---|
| Myeloma IX26 | T (50–100 mg/day to PD) vs. no maintenance post ASCT | 245 vs. 247 | 38 monthsa | 9 months |
Median PFS: 30 vs. 23 months (HR 1.42) 3-year OS: 75% vs. 80% |
Discontinuation due to AEs: 52.2%a Serious adverse reaction: 8.5% |
| Meta-analysis, T (various doses/durations) vs. no T maintenance, inc. non-ASCT | 1098 vs. 1333 | NR | NR |
OS: HR 0.75 7-year OS: 12.3% difference in rate, in favor of T maintenance |
NR | |
| HOVON-5027,29 | TAD-ASCT-T (50 mg/day to PD) vs. VAD-ASCT-IFN | 268 vs. 268 |
Initial analysis: 52 months Follow-up: 129 months |
NR |
Median EFS: 34 vs. 22 months (HR 0.60); HR 0.62 at follow-up Median PFS: 34 vs. 25 months (HR 0.67) OS: HR 0.96 OS from relapse: 20 vs. 31 months (HR 1.50) |
T maintenance: Discontinuation due to AEs: 33%; 42% at follow-up (vs. 27% IFN) Grade 1/2/3/4 PN: 21/33/9/1% |
| NCIC-CTG Myeloma 1028 | TP (T 200 mg/day, P 50 mg Q2d; up to 4 yrs) vs observation post ASCT | 166 vs. 166 | 4.1 years | 16.1 vs. 14.9 months |
4-year PFS: 32% vs. 14% (HR 0.55) 4-year OS: 68% vs. 60% (HR 0.77) Median OS post-relapse: 27.7 vs. 34.1 months |
Grade 3/4 thromboembolism: 7.3% vs. 0 Grade 3/4 sensory PN: 9.6% vs. 1.2% |
| IMWG meta-analysis, six studies30 | T (various doses/durations) vs. no T maintenance, inc. non-ASCT | 1276 vs. 1510 | NR | NR |
PFS: HR 0.65 OS: HR 0.84 |
NR |
| CALGB 10010433–35 | R (10 mg/day to PD) vs. placebo post ASCT | 231 vs. 229 | Initial report: 34 months | NR |
Median PFS/TTP: 46 vs. 27 months (HR 0.48) 3-year OS: 88% vs. 80% (HR 0.62) |
Grade 3/4 AEs: 32%/16% vs. 12%/5% Grade 3/4 neutropenia: 32%/13% vs. 12%/3% Discontinuation due to AEs: 10% |
| Follow-up: 91 months | 31.0 vs. 18.1 months |
Median PFS/TTP: 57.3 vs. 28.9 months (HR 0.57) Median OS: 113.8 vs. 84.1 months (HR 0.61) Median OS post-relapse: 42.6 vs. 39.2 months (HR 0.83) |
Grade 3/4 neutropenia: 50% vs. 18% Discontinuation due to AEs: 18% Heme/solid/non-invasive SPMs: 8%/6%/5% vs. 1%/4%/3% |
|||
| R (10 mg/day to PD) vs. placebo post ASCT, adjusted for crossover | 76 placebo patients crossed over to R | Updated: >91 months | NR |
Median OS: ITT, unadjusted: 111.01 vs. 80.26 months, HR 0.61 RPSFTM adjustment for crossover: 111.01 vs. 70.96 months, HR 0.52 |
NR | |
| IFM2005-0236 | R (10–15 mg/day to PD) vs. placebo post ASCT | 307 vs. 307 | 45 months | NR |
≥ VGPR (randomization-to-post-maintenance): 61−84% vs. 59−76% 4-year PFS: 43% vs. 22% (HR 0.50) 4-year OS: 73% vs. 75% (HR 1.06) |
Grade 3/4 hematologic AEs: 58% vs. 23% (neutropenia 51% vs. 18%) Discontinuation due to AEs: 27% vs. 15% SPMs: 3.1 vs. 1.2 ppya100 |
| GIMEMA RV-MM-PI-20937 | R (10 mg, d 1–21, 28-d cycles, to PD) vs. no maintenance post-MPR (n = 132) or ASCT (n = 141) consolidation |
126 vs. 125 (67 vs. 68 post ASCT) |
51.2 months from enrollment | NR |
ASCT-R vs. ASCT: Median PFS: 54.7 vs. 37.4 months 5-year OS: 78.4% vs. 66.6% R maintenance CR rate improvement: 15.7 to 35.7% R vs. no maintenance, post-MPR/ASCT Median PFS: 41.9 vs. 21.6 months (HR 0.47) OS: HR 0.64 |
R vs. no maintenance, post-MPR/ASCT Grade 3/4 AEs: Neutropenia 23.3% vs. 0% Infections 6.0% vs. 1.7% Dermatologic events 4.3% vs. 0% Discontinuation due to AEs: 5.2% vs. 0% |
| Phase 3 meta-analysis (above three trials)32 | R (doses as per above three trials) vs. placebo/no maintenance post ASCT | 605 vs. 603 | 79.5 months | Mean 28 vs. 22 months |
Median PFS: 52.8 vs. 23.5 months (HR 0.48) Median PFS2: 73.3 vs. 56.7 months (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 XI25,40 | R (10/25 mg, d 1–21, 28-d cycles, to PD) vs. observation post ASCT | 730 vs. 518 | 31 monthsb | 18 cycles (4-week cycles)b |
Cumulative rate of response improvement at 60 months: 15.8% vs. 11.0% Median PFS: 57 vs. 30 months (HR 0.48) Median PFS2: not reached vs. 59 months (HR 0.57) 3-year OS: 87.5% vs. 80.2% (HR 0.69) |
Grade 3/4 neutropenia: 28%/5%b Discontinuations due to AEs: 28%b SPMs: 5.3% vs. 3.1%b |
| NCT0109183141 | RP (R 10 mg, d 1–21, 28-d cycles; P 50 mg, Q2d; to PD) vs. R alone post ASCT | 60 vs. 57 | 41.0 vs. 42.3 monthsc | Median 28.9 vs. 25.3 monthsc |
Data from enrollment (including ASCT): Median PFS: 37.6 vs. 31.5 months 4-year OS: 77% vs. 75% |
Grade 3/4 AEs:c Neutropenia: 8% vs. 13% Infections: 8% vs. 5% Discontinuations due to AEs: 5% vs. 8% |
| GMMG-MM560 | R (10–15 mg/d) → 2 yrs vs. R (10–15 mg/d) → CR post-PAD/VCD + ASCT | PAD-R → 2 yrs vs. VCD-R → 2 yrs vs. PAD-R → CR vs. VCD–R → CR: 125 vs. 126 vs. 126 vs. 125 | 60.1 months |
74% vs. 75% vs 39% vs. 50% received maintenance 35% vs. 35% vs 14% vs. 18% completed 2 years |
Median PFS: 43.2 vs. 40.9 vs. 35.9 vs. 35.7 months 36-month OS: 83% vs. 85% vs 75% vs. 77% |
Rates of grade ≥ 3 AEs and grade ≥ 2 infections, cardiac disorders, neuropathy, and thromboembolic events: 87.3% vs. 91.3% vs. 79.5% vs. 77.4% AEs during maintenance (R → 2 years vs. R → CR): 77.6% vs. 58.2% Grade ≥ 2 infections (R → 2 years vs. R → CR): 52.7% vs. 32.3% |
| HOVON-65/GMMG-HD452,53 | PAD-ASCT-V (1.3 mg/m2 IV, Q2w, up to 2 yrs) vs. VAD-ASCT-T (50 mg/day, up to 2 yrs) |
413 vs. 414 (270 vs. 230 maintenance) |
Initial analysis: 41 months | 47% vs. 27% received 2 years of maintenance |
Response improvement during maintenance: 23% vs. 24% Median PFS: 35 vs. 28 months (HR 0.75) Median PFS from last ASCT: 31 vs. 26 months 5-year OS: 61% vs. 55% (HR 0.81) |
During maintenance: Grade 3/4 AE: 48% vs. 46% Grade 3/4 infections: 24% vs. 18% New-onset grade 3/4 PN: 5% vs. 8% Discontinuation due to toxicity: 11% vs. 30% |
| Updated analysis: 96 months | 50% vs. 28% received 2 years of maintenance |
Median PFS: 34 vs. 28 months (HR 0.76) Median OS: 91 vs. 82 months (HR 0.89) Median OS from relapse: 43 vs. 40 months (HR 1.02) |
SPMs: 7% vs. 7% | |||
| GEM05MENOS6554 | VT (V 1.3 mg/m2 IV, d 1, 4, 8, 11, Q3M; T 100 mg/day) vs. T (T 100 mg/day) vs. IFN (3 MU × 3 per week) post ASCT, for up to 3 yrs | 91 vs. 88 vs. 92 | 58.6 months | 2.05 vs. 1.6 vs. 1.55 years |
Improvement in CR rate: 21% vs. 11% vs. 17% Median PFS: 50.6 vs. 40.3 vs. 32.5 months 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-MM358 | Ixazomib (3–4 mg, d 1, 8, 15, 28-d cycles; up to 2 yrs) vs. placebo post ASCT | 395 vs. 261 | 31 months | 25 vs. 22 4-week cycles |
Response improvement: 46% vs. 32% (RR 1.41) Median PFS: 26.5 vs. 21.3 months (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, ASCT autologous stem cell transplant, CR complete response, d day(s), DoT duration of treatment, EFS event-free survival, GI gastrointestinal, heme hematologic, HR hazard ratio, IMWG International Myeloma Working Group, IFN interferon, inc. including, IV intravenous, MPR melphalan-prednisone-lenalidomide, MU million units, NR not reported, OS overall survival, P prednisone, PAD bortezomib-doxorubicin-dexamethasone, PD progressive disease, PFS progression-free survival, PFS2 progression-free survival from start of treatment to progression on next line of treatment, PN peripheral neuropathy, ppy*100 per 100 patient-years, Q2d every other day, Q2w every 2 weeks, Q3M every 3 months, R lenalidomide, RP lenalidomide-prednisone, RPSFTM rank-preserving structural failure time model, RR relative risk, SPMs second primary malignancies, T thalidomide, TAD thalidomide-doxorubicin-dexamethasone, TP thalidomide-prednisone, TTP time to progression, V bortezomib, VAD vincristine-doxorubicin-dexamethasone, VGPR very good partial response, VT bortezomib-thalidomide, wk week, yrs years.
aData shown for all 408 vs. 410 patients randomized to maintenance, not just post-ASCT intensive pathway.
bOverall data in 1137 vs. 834 patients randomized to lenalidomide vs. observation across both the transplant-eligible and transplant-ineligible pathways.
cOverall data in 117 vs. 106 patients randomized to lenalidomide-prednisone vs. lenalidomide maintenance across the CRD and ASCT consolidation arms.