Table 1.
Major clinical trials and real-world studies based on lenalidomide in first-line treatment.
| Setting | Study | Age* | Prior therapy | Response ORR/≥VGPR/≥CR | >PFS/OS/DOT/TTP | Toxicity, G≥3 |
|---|---|---|---|---|---|---|
| MAJOR CLINICAL TRIALS | ||||||
|
First line,
NTE patients |
FIRST (13, 16) Rd vs MPT: N=1623 Rd (until PD): 535 Rd (18 cycles): 541 |
73 | – | Rd (until PD): - 75%/44%/15% Rd (18 cycles): - 73%/43/14% |
Rd (until PD): - mPFS: 26 mo - mOS: 59 mo Rd (18 cycles): - mPFS: 21 mo - mOS: 62 mo |
Rd (until PD): - Anemia 18% - Neutropenia 28% - Infection 29% - Pneumonia 8% Rd (18 cycles): - Anemia 16% - Neutropenia 26% - Infection 22% - Pneumonia 8% |
|
First line,
NTE patients |
MAIA (12) Dara-Rd vs. Rd, N=737 |
73 | – | Dara-Rd: - 92%/79%/48% Rd: - 81%/53%/25% |
Dara-Rd: - PFS: 32 mo - mOS: NR (FU 28 mo) Rd: - mPFS: 32 mo - mOS: NR (FU 28 mo) |
Dara-Rd vs. Rd: - Anemia 11% vs. 19% - Neutropenia 50% vs. 35% - Infection 32% vs. 23% - Pneumonia 14% vs. 8% |
|
First line,
NTE patients |
SWOG S0777 (15) VRd vs. Rd, N=525 |
63 | – | VRd vs. Rd: - 82%/43%/16% - 72%/32%/86% |
VRd vs. Rd: - mPFS: 43 vs. 30 mo - mOS: 75 vs. 64 mo |
VRd vs. Rd: - Hematologic AEs 47% vs. 32% - Infection 14% vs. 14% |
|
First line,
NTE patients |
ENDURANCE (17) VRd vs. KRd, N=1053 |
64 | – | VRd: - 84%/65%/15% KRd: - 87%/74%/18% |
VRd vs. KRd: mPFS: 34.4 vs. 36.6 mo mOS: NR vs. NR 3-y OS rate: 86% vs. 84% |
- PN 8% vs. <1% - VTE 2% vs. 5% |
|
First line,
TE patients |
IFM 2009 (18) VRd-ASCT-VRd: N=350 |
60 | – | - 98%/88%/59% | mPFS: 50 mo mOS: NR 4-y OS rate: 81% |
- Neutropenia 92% - Anemia 20% - Thrombocytopenia 83% - Infection 20% - PN 13% - SPM 1.5% |
| Post-ASCT maintenance |
RV-MM-PI-209 (19) R vs. no R: N=251 |
57 | Len-exposed: 100% | – | mPFS: 41.9 mo 3-y OS rate: 88% |
- Neutropenia 27% - Infection 7% - Dermatologic AEs 5% - Discontinuation 6% R vs. no R: - SPM 5% vs. 5% |
| Post-ASCT maintenance |
IFM2005-02 (20) R vs. placebo: N=614 |
55 | Bort-exposed: 92% | – | mPFS: 41 mo 4-y OS rate: 73% |
- Discontinuation 27.1% R vs. no R: - SPM 8% - 5-y SPM 3.1% vs 1.2% |
| Post-ASCT maintenance |
CALGB 100104 (7) R vs. placebo: N =460 |
59 | Bort-exposed: 42% Len-exposed: 34% |
– | TTP: 46 mo 3-y OS rate: 88% |
- Discontinuation 9% R vs. no R: - SPM 8% vs. 3% |
| Post-ASCT maintenance |
McCarthy et al., 2017: meta-analysis (21) R vs. placebo/observation: N=1208 |
58 | Bort-exposed: 39% Len-exposed: 22% |
– | PFS: 52.8 mo 7-y OS rate: 62% mOS: NR |
- Discontinuation 29.1% R vs. no R: - Hematologic SPM 5.3% vs. 0.8%** - Solid SPM 5.8% vs. 2%** |
| Post-ASCT maintenance |
Myeloma XI (22) R vs. observation: N=1981 |
66 | Len-exposed: 63% | – | mPFS: 39 mo 5-y OS: 61 mo |
- Neutropenia 33% - Discontinuation 52% (28% due to AE) R vs. no R: - SPM 2.4% vs. 1.4% |
| MAJOR REAL-WORLD STUDIES | ||||||
|
First line,
NTE patients |
Cejalvo et al., 2021 (23) Rd: N=24 Other: N=651 |
75.6 | – | – | mPFS: 20 mo mOS: 34.6 mo |
NA |
|
First line,
NTE patients |
Canadian Myeloma Research Group database (CMRG-DB), Jimenez-Zepeda et al., 2021 (24) Rd: N=208 Other: N=948 |
75 | – | - 87%/61%/28% | mPFS: 28 mo mOS: 66 mo |
NA |
|
First line,
NTE patients |
Zamagni et al., 2021 (25) Rd: N=194 Other: N=233 |
74 | – | – | mPFS: 38 mo mOS: NA |
NA |
|
First line,
NTE patients |
Chari et al., 2019 (26) Rd: N=814 VRd: N=319 |
Rd vs. VRd: 70 vs. 64 |
– | – | Rd vs. VRd: - mTTNT: 36.7 vs. 37.5 mo - DOT: 12 vs. 14.8 mo |
NA |
|
First line,
NTE patients |
EMMY, Decaux et al., 2021 (27) Rd: N=162 VRd: N=158 |
Rd vs. VRd: 79.6 vs. 69.3 |
– | – | Rd vs. VRd: - mTTNT: 29 vs. 24 mo - mTTNT, age <75 y: 29.4 vs. 34.7 mo - mTTNT, age ≥75 y: 29.5 vs. 17.1 mo - 2-y OS rate: 86% vs. 85% |
NA |
|
First line,
TE patients |
Joseph et al., 2020 (28) N=1000 |
61 | – | - 97%/90%/33% | mPFS: - 65 mo - ISS I vs. III: 73 vs. 50 mo - R-ISS I vs. III: 129 vs. 31 mo mOS: - 127 mo - ISS I vs. III: 89 vs. 95 mo - R-ISS I vs. III: NR vs. 60 mo |
NA |
| Post-ASCT maintenance |
Canadian Myeloma Research Group database (CMRG-DB), Cherniawsky et al., 2021 (29) R vs. no R: N=723 vs. 533 |
NA | Bort-exposed: 100% Len-exposed: 1% |
– | mPFS: 58.2 mo 5-y OS rate: 81% mOS: NR (>124 mo) |
- Discontinuation 20% R vs. no R: - SPM 3.4% vs. 6.4% |
| Post-ASCT maintenance |
Chakraborty et al., 2018 (30) R vs. no R: N=132 vs. 341 |
61 | PI-based: 34% IMiD-based: 26% PI+IMiD-based: 40% |
– | mPFS: 36.5 mo 4-y OS rate: 79% - R: ISS I/II vs. III, OS rate: 85% vs. 73% - No R: ISS I/II vs. vs. III, OS rate: 84% vs. 68% |
- Discontinuation 17% R vs. no R: 7-y SPM 5.4% vs. 6.4% |
| Post-ASCT maintenance |
Connect MM Registry, Jagannath et al., 2018 (31) R vs. no R: N=213 vs. 165*** Other maintenance therapies: 54 |
60 | Bort-exposed: 97% Len-exposed: 45% |
– | mPFS: 50.3 mo 3-y PFS rate: 50.8% mOS: NR 3-y OS rate: 85% |
- Discontinuation 19% R vs. no R: - SPM 4.7% vs. 6.1% |
*Age: median age. **Frequency evaluated before progressive disease (follow-up: 70.5 months). ***Induction strategies and percentage calculated for the entire cohort population (N=432).
RW, real world; TE, transplant-eligible; NTE, non-transplant-eligible; ASCT, autologous stem-cell transplantation; R, Len, lenalidomide; d, dexamethasone; Dara, daratumumab; V, Bort, bortezomib; K, carfilzomib; ORR, overall response rate; ≥VGPR, at least a very good partial response; ≥CR, at least a complete response; PD, progressive disease; NA, not available; mo, months; y, years; FU, follow-up; NR, not reached: PI, proteasome inhibitor; IMiD, immunomodulatory drug; PFS, progression-free survival; OS, overall survival; mPFS, median PFS; mOS, median OS; DOT, duration of treatment; TTNT, time to next treatment; mTTNT, median TTNT; ISS, International Staging System stage; R-ISS, Revised ISS stage; G, grade, PN, peripheral neuropathy; VTE, venous thromboembolism; SPM, second primary malignancy.