Rapid Progress in the Use of Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in the Treatment of Multiple Myeloma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Mechanism of Action of Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in the Treatment of Multiple Myeloma
3. Immunomodulatory Drugs in Newly Diagnosed Multiple Myeloma
3.1. Thalidomide
3.1.1. Thalidomide for the Treatment of Newly Diagnosed Multiple Myeloma in Patients Eligible for ASCT
3.1.2. Thalidomide for the Treatment of Newly Diagnosed Multiple Myeloma in Patients Ineligible for ASCT
3.2. Lenalidomide
3.2.1. Lenalidomide for the Treatment of Newly Diagnosed Multiple Myeloma in Patients Eligible for ASCT
3.2.2. Lenalidomide in the Treatment of Newly Diagnosed Multiple Myeloma in Patients Ineligible for ASCT
4. Immunomodulatory Drugs in Maintenance Therapy after ASCT
4.1. Thalidomide
4.2. Lenalidomide
5. Immunomodulatory Drugs in the Treatment of Relapsed/Refractory Multiple Myeloma
5.1. Thalidomide
5.2. Lenalidomide
5.3. Pomalidomide
6. The New Generation of Immunomodulatory Drugs—Cereblon E3 Ligase Modulators
6.1. Iberdomide (CC-220)
6.2. Avadomide (CC-122)
6.3. CC-92480
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Trial/Author | Regimen | Patients, n | ORR, % | ≥VGPR, % | Median PFS, mo or % | Median OS, mo or % |
---|---|---|---|---|---|---|
Transplant eligible | ||||||
Thalidomide-based | ||||||
Cavo et al. [39] | TD | 238 | 87 | 31 | NR; 60% at 36 mo | NR; 88% at 36 mo |
VTD | 236 | 96 | 62 | NR; 48% at 36 mo | NR; 90% at 36 mo | |
Moreau et al. [40] | VCD | 169 | 83 | 56 | NR | NR |
VTD | 169 | 92 | 66 | NR | NR | |
CASSIOPEIA [42] | Dara-VTD | 543 | 92 | 83 | NR; 93% at 18 mo | NR |
VTD | 542 | 90 | 78 | NR; 85% at 18 mo | NR | |
Lenalidomide-based | ||||||
ENDURANCE [44] | VRd | 542 | 84 | 65 | 34.4 | NR; 84% at 36 mo |
KRd | 545 | 87 | 74 | 34.6 | NR; 86% at 36 mo | |
Transplant ineligible | ||||||
Thalidomide-based | ||||||
Palumbo et al. [45] | MPT | 167 | 69 | 45 | 21.8 | 45.0 |
MP | 164 | 48 | 15 | 14.5 | 47.6 | |
Palumbo et al. [46] | VMPT-VT | 254 | 89 | 59 | 35.3 | NR; 61% at 60 mo |
VMP | 257 | 81 | 50 | 24.8 | NR; 51% at 60 mo | |
Lenalidomide-based | ||||||
Rajkumar et al. [47] | RD | 223 | 79 | NR | NR | NR; 75% at 24 mo |
Rd | 225 | 68 | NR | NR | NR; 87% at 24 mo | |
SWOG S0777 [48] | Rd | 261 | 79 | 53 | 29 | 69 |
VRd | 264 | 90 | 75 | 41 | NR; 69% at 60 mo | |
FIRST [49] | Rd (cont) | 535 | 81 | 48 | 26 | 59 |
Rd18 | 541 | 79 | 47 | 21 | 62 | |
MPT | 547 | 67 | 30 | 22 | 49 | |
MM-015 [50] | MPR-R | 152 | 77 | 77 | 31 | NR; 70% at 36 mo |
MPR | 153 | 68 | 68 | 14 | NR; 62% at 36 mo | |
MP | 154 | 50 | 50 | 13 | NR; 66% at 36 mo | |
ECOG E1A06 [51] | MPT-T | 154 | 75 | 25 | 21 | 52.6 |
MPR-R | 152 | 70,4 | 32 | 19 | 47.7 | |
MAIA [52] | Rd | 369 | 82 | 57 | 34 | NR |
Dara-Rd | 368 | 93 | 81 | NR; 60% at 48 mo | NR |
Trial/Author | Regimen | Patients, n | ORR, % | ≥VGPR, % | Median PFS, mo | Median OS, mo or % |
---|---|---|---|---|---|---|
Lenalidomide-based | ||||||
ASPIRE [90] | KRd | 396 | 87.1 | 70 | 26 | 48.3 |
Rd | 396 | 66.7 | 40 | 17,6 | 40.4 | |
TOURMALINE-MM1 [91] | Ixa-Rd | 360 | 78 | 48 | 20.6 | N/A |
Rd | 362 | 72 | 39 | 14.7 | N/A | |
POLLUX [92] | Dara-Rd | 286 | 93 | 80.4 | 44.5 | NR |
Rd | 283 | 76.4 | 49.3 | 17.5 | NR | |
ELOQUENT-2 [93] | Elo-Rd | 321 | 79 | 36 | 18.5 | 43.7 |
Rd | 325 | 66 | 30 | 15 | 39.6 | |
Pomalidomide-based | ||||||
NIMBUS [94] | Pd | 302 | 31 | 7 | 4 | 12.7 |
Dex | 153 | 10 | 1 | 1.9 | 8.1 | |
Baz et al. [95] | PCD | 34 | 65 | 12 | 9.5 | N/A |
Pd | 36 | 39 | 14 | 4.4 | 16.8 | |
OPTIMISMM [96] | PVd | 281 | 82 | 52.7 | 11.2 | NR |
Vd | 278 | 50 | 18.3 | 7.1 | NR | |
APOLLO [97] | Dara-Pd | 151 | 69 | 51 | 12.4 | NR |
Pd | 153 | 46 | 20 | 7 | NR | |
ICARIA-MM [98] | Isa-Pd | 154 | 60 | 32 | 11.5 | NR; 72% at 12 mo |
Pd | 153 | 35 | 9 | 6.5 | NR; 63% at 12 mo | |
ELOQUENT-3 [99] | Elo-Pd | 60 | 53 | 20 | 10.3 | NR |
Pd | 57 | 26 | 9 | 4.7 | NR |
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Charliński, G.; Vesole, D.H.; Jurczyszyn, A. Rapid Progress in the Use of Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in the Treatment of Multiple Myeloma. Cancers 2021, 13, 4666. https://doi.org/10.3390/cancers13184666
Charliński G, Vesole DH, Jurczyszyn A. Rapid Progress in the Use of Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in the Treatment of Multiple Myeloma. Cancers. 2021; 13(18):4666. https://doi.org/10.3390/cancers13184666
Chicago/Turabian StyleCharliński, Grzegorz, David H. Vesole, and Artur Jurczyszyn. 2021. "Rapid Progress in the Use of Immunomodulatory Drugs and Cereblon E3 Ligase Modulators in the Treatment of Multiple Myeloma" Cancers 13, no. 18: 4666. https://doi.org/10.3390/cancers13184666