Introduction
Key clinical trials of lenalidomide in NDMM
Lenalidomide as first-line therapy in patients ineligible for, or not scheduled for immediate, transplantation
First-line regimen | PFS, mths | HR (95% CI) for PFS vs. continuous or FD Rd, or MPR-R | OS | HR (95% CI) for OS vs. continuous or FD Rd, or MPR-R | |
---|---|---|---|---|---|
RV-MM-PI-209a [10] Median follow-up: 51 mths | Rd-MPR-R (4 cycles Rd, 6 cycles MPR, continuous R) (n = 59) | Median: 34.2 | 5 years: 70.2% | ||
Rd-MPR (4 cycles Rd, 6 cycles MPR) (n = 57) | 21.8 | 58.7% | |||
Rd-ASCT-R (4 cycles Rd, HDM+ASCT, continuous R) (n = 67) | 54.7 | 0.44 (0.32–0.61); p < 0.001 for HDM+ASCT±R vs. MPR±R | 78.4% | 0.55 (0.32–0.93); p = 0.02 for HDM+ASCT±R vs. MPR±R at 4 years (81.6% vs. 65.3%) | |
Rd-ASCT (4 cycles Rd, HDM+ASCT) (n = 68) | 37.4 | 66.6% | |||
SWOG S0777a [16] Median follow-up: 55 mths | Rd-R, 6 cycles (n = 261) | Medianc: 30 | 0.71d (0.56–0.91); 1-sided p = 0.0018 for Rd-R vs. VRd-R | Median: 64 mths | 0.709 (0.52–0.96); 2-sided p = 0.0250 for Rd-R vs. VRd-R |
VRd-R, 8 cycles (n = 264) | 43 | 75 mths | |||
FIRSTb [22, 24] Median follow-up: 67 mths | Continuous Rd (n = 535) | Median: 26.0 | 0.70 (0.60–0.81) | Median: 59.1 mths | 1.02 (0.86–1.20) |
Rd, 18 cycles (n = 541) | 21.0 | 0.69 (0.59–0.79); p < 0.00001 | 62.3 mths | 0.78 (0.67–0.92); p = 0.0023 | |
49.1 mths | |||||
MPT, 18 cycles (n = 547) | 21.9 | ||||
MM-015b [23] Median follow-up: 30 mths | MPR-R (9 cycles MPR, continuous R) (n = 152) | Median: 31 | 3 years: 70% | ||
MPR, 9 cycles (n = 153) | 14 | 0.49; p < 0.001 | 62% | 0.79; p = 0.25 | |
MP, 9 cycles (n = 154) | 13 | 0.40; p < 0.001 | 66% | 0.95; p = 0.81 | |
EMN 01b [26] Median follow-up: 39 mths | Rd, 9 cycles (n = 217) | Median: 21 | 4 years: 58% | ||
CPR, 9 cycles (n = 220) | 20 | 1.01 (0.90–1.13); p = 0.938 for CPR vs. Rd | 68% | 0.93 for CPR vs. Rd | |
MPR, 9 cycles (n = 217) | 24 | 65% | 1.02 for MPR vs. Rd | ||
0.81 (0.63–1.02); p = 0.081 for MPR vs. Rd | |||||
RV-MM-PI-0752b [27] Median follow-up: 25 mths | Continuous Rd (n = 101) | 20 mths: 42% | 20 mths 79% | ||
Rd-R (9 cycles Rd, continuous R) (n = 98) | 43% | 0.93 (0.64–1.34); p = 0.681 | 84% | 0.73 (0.40–1.33); p = 0.306 | |
MAIAb [25] Median follow-up: 28 mths | Continuous Rd (n = 369) | Median: 31.9 | Median: NR | ||
Continuous DRd (n = 368) | NR | 0.56 (0.43–0.73); p < 0.001 | NR | Not reported |
Lenalidomide as maintenance therapy following transplantation
CALGB 100104 [30, 32] Median follow-up: 91 mths | IFM-2005-02 [29] Median follow-up: 45 mths | Meta-analysis of CALGB 100104, IFM-2005-02, and GIMEMA RV-MM-PI-209 [33] Median follow-up: 79.5 mths | Myeloma XI [31] Median follow-up: 31 mths | |||||
---|---|---|---|---|---|---|---|---|
Maintenance therapy | Lenalidomide | Placebo | Lenalidomide | Placebo | Lenalidomide | Placebo or observation | Lenalidomide | Observation |
n = 231 | n = 229 | n = 307 | n = 307 | n = 605 | n = 603 | n = 1137 | n = 834 | |
Median TTP/PFS, mths | TTP: 57.3 | TTP: 28.9 | PFS: 41 | PFS: 23 | PFS: 52.8 | PFS: 23.5 | PFS: 39 | PFS: 20 |
HR (95% CI) | 0.57 (0.46–0.71); p < 0.0001 | 0.50; p < 0.001 | 0.48 (0.41–0.55); p = NR | 0.46 (0.41–0.53); p < 0.0001 | ||||
OS | Median: 113.8 mths | Median: 84.1 mths | 4 years: 73% | 4 years: 75% | Median: NR | Median: 86.0 mths | 5 years: 61.3% | 5 years: 56.6% |
HR (95% CI) | 0.61 (0.46–0.80); p = 0.0004 | Not reported; p = 0.70 | 0.75 (0.63–0.90); p = 0.001 | 0.87 (0.73–1.05); p = 0.15 |
Lenalidomide as first-line therapy in NDMM patients ineligible for ASCT: patient selection and dosing
Patient selection
Dosing and treatment duration
Use of lenalidomide as maintenance therapy
Patient selection
Dosing
Determining the optimal duration of lenalidomide maintenance treatment
Management of hematologic AEs
Neutropenia
AE, % | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
First-line regimen | Neutropenia | Anemia | Thrombocytopenia | Fatigue | Diarrhea | Constipation | Infection | Cardiac disorder | Dermatologic AE | DVT | PE | SPM | |
FIRST [22, 24 Median follow-up: 67 months | Continuous Rd (n = 532) | 30 | 19 | 9 | NR | 5 | 2 | 32 | NR | NR | 5 | 4 | 7 |
Rd, 18 cycles (n = 540) | 26 | 16 | 8 | NR | 3 | 2 | 22 | NR | NR | 4 | 3 | 7 | |
MPT, 18 cycles (n = 541) | 45 | 19 | 11 | NR | 1 | 5 | 17 | NR | NR | 3 | 4 | 9 | |
MM-015a [23] Median follow-up: 30 months | MPR-R (9 cycles MPR, continuous R) (n = 150) | 67/35 | 24/3 | 35/11 | 5/0 | 2/1 | NR | 9/1 | 3/2 | 5/0b | 1/0 | NR | 3-year risk: 7 |
MPR, 9 cycles (n = 152) | 64/32 | 26/3 | 38/12 | 1/1 | 1/0 | NR | 13/2 | 3/3 | 5/0b | 4/1 | NR | 7 | |
MP, 9 cycles (n = 153) | 29/8 | 14/1 | 12/4 | 3/0 | 0/0 | NR | 7/0 | 3/0 | 1/0b | 1/0 | NR | 3 | |
EMN 01a [26] Median follow-up: 39 months | Rd, 9 cycles (n = 212) | 25 | 4 | 7 | 2 | NR | NR | 9 | 6 | 5 | 2c | NR | 0 |
CPR, 9 cycles (n = 220) | 29 | 6 | 9 | 2 | NR | NR | 7 | 6 | 8 | 5c | NR | 1 | |
MPR, 9 cycles (n = 211) | 64 | 15 | 18 | 3 | NR | NR | 11 | 5 | 5 | 3c | NR | 2 | |
RV-MM-PI-0752 [27] Median follow-up: 25 months | Continuous Rd (n = 101) | 14 | NR | NR | NR | NR | NR | 11 | NR | 7d | NR | NR | NR |
Rd-R (9 cycles Rd, continuous R) (n = 98) | 17 | NR | NR | NR | NR | NR | 9 | NR | 3d | NR | NR | NR | |
MAIA [25] Median follow-up: 28 months | Continuous Rd (n = 369) | 35 | 20 | NR | 4 | 4 | 0 | 23 | NR | NR | NR | NR | 7 |
Continuous DRd (n = 368) | 50 | 12 | NR | 8 | 7 | 2 | 32 | NR | NR | NR | NR | 8 |
CALGB 100104 [30] Median follow-up: 91 months | IFM-2005-02 [29] Median follow-up: 45 months | Myeloma XI [31] Median follow-up: 31 months | |||||
---|---|---|---|---|---|---|---|
Lenalidomidea | Placebo (no crossover)a | Placebo (crossover)a,b | Lenalidomide | Placebo | Lenalidomidea | Observation | |
n = 231 | n = 143 | n = 86 | n = 306 | n = 302 | n = 1137 | n = 834 | |
Neutropenia | 35/15 | 5/3 | 30/5 | 51 | 18 | 28/5 | NR |
Anemia | 4/1 | 0/0 | 1/0 | 3 | 2 | 4/1 | NR |
Thrombocytopenia | 10/5 | 0/5 | 3/2 | 14 | 7 | 4/2 | NR |
Fatigue/lethargy | 0/0 | 0/0 | 0/0 | 5 | 2 | 1/0 | NR |
Diarrhea | 5/0 | 1/0 | 3/0 | 2 | < 1 | NR | NR |
Constipation | NR | NR | NR | 1 | 0 | < 1/0 | NR |
Infection | 6/1 | 2/0 | 5/0 | 13 | 5 | 11/1 | NR |
Cardiac disorder | NR | NR | NR | NR | NR | 0/0 | NR |
Rash | 4/0 | 1/0 | 1/0 | 3 | 2 | 1/< 1 | NR |
Thromboembolic event | NR | NR | NR | 2/1c | 1/0c | NR | NR |
Second primary malignancyd, % | 19 | 3 | 15 | 10 | 4 | 5/3e | NR |