Use of MRD in clinical practice and to make treatment decisions
| Study . | Number of patients and characteristics . | Chemotherapy . | MRD technique and limit of detection . | MRD-related outcomes . |
|---|---|---|---|---|
| MRD for evaluating treatment efficacy | ||||
| PETHEMA/GEM2012 trial randomized phase 3 study NCT01916252 Paiva et al26 | N = 458 TE NDMM | Induction VRd (×6) ASCT Consolidation VRd (×2) | NGF median, 3 × 10−6 | MRD– status after induction, 28%
|
| UK OPTIMUM /MUKnine trial phase 2 study NCT03188172 Kaiser et al27 | N = 95 ultrahigh-risk NDMM | Induction D-CVRd (×6) ASCT Consolidation D-CVRd (×6) D-VR (×12) Maintenance D-R | MFC, 10−5 | MRD status on day +100 after ASCT: MRD–, 64% MRD+, 14% MRD not evaluable, 22% |
| GMMG-HD7 study randomized phase - study NCT03617731 Goldschmidt et al28 | N = 662 TE NDMM | Induction: VRd ± I | NGF, 10−5 | After induction: MRD– status:
|
| MRD for comparing the efficacy of different treatment approaches | ||||
| CASSIOPEIA randomized phase 3 study NCT02541383 Moreau et al29 | N = 1085 TE NDMM | Induction D-VTd vs VTd (×4) ASCT Consolidation VTd vs VTd (×2) Maintenance D vs observation | MFC, 10−5 | Day +100 after ASCT: MRD– status:
|
| BENEFIT: IFM2020-05 randomized phase 3 study NCT04751877 Leleu et al30 | N = 270 TIE, nonfrail NDMM | Isa-VRD vs Isa-Rd | NGS, 10−5 | Primary end point: MRD at 18 mo (ongoing) |
| EMN28/CARTITUDE-6 randomized phase 3 study NCT0525708331 | N = 750 TE NDMM | cilta-cel vs ASCT | NGS, 10−5 | Dual primary end points: PFS and sustained MRD |
| MRD for adapting therapy | ||||
| MIDAS randomized phase 3 study NCT04934475 Moreau32 | N = 716 TE NDMM | Induction Isa-KRd (×6) Standard risk (NGS, <10−5): arm A; 6 additional cycles of Isa-KRd vs arm B: ASCT followed by 2 cycles of Isa-KRd; High risk (NGS, >10−5): arm C: ASCT followed by 2 cycles of Isa-KRd vs arm D: tandem ASCT | NGS, 10−5 | Randomization based on MRD assessment after induction |
| MRD for adapting maintenance therapy and duration | ||||
| EMN017/MMY3014 (Perseus) randomized phase 3 NCT0371060333 | N = 690 TE NDMM | Induction: D-VRd vs VRd (×4) ASCT Induction: D-VRd vs VRd (×2) Maintenance DR vs R until progression | NGS, 10−5 | D-VRD arm : 12 mo sustained MRD and ≥ 2 y maintenance: D interruption |
| GEM2014 trial randomized phase 3 study NCT02406144 Rosinol et al34 | N = 316 TE NDMM | Maintenance ixazomib-Rd vs Rd for 2 y | NGF, 3 × 10−6 | At 2 y. MRD– status: maintenance interruption MRD+ status: pursue Rd alone for 3 more years |
| MRD for introduction of ERI | ||||
| REMNANT trial randomized phase 2/3 study NCT04513639 Askeland et al35 | N = 176 TE NDMM | Induction VRd (×4) ASCT (×1 or 2) Consolidation VRd (×2) | NGF, 10−5 | For patients with MRD– status: randomization
|
| GEM-TECTAL trial phase 2 study NCT0584961036 | N = 30: high risk, R-ISS-III, TE, and fit TIE NDMM | Induction D-VRd (×4) Intensification: D-teclistamab (×6) | NGF, 10−6 | MRD assessment after intensification: MRD– status: D-teclistamab 2y. MRD+ status or not in CR: D – talquetamab, and after 6 cycles: MRD– status, pursue for 2 y; MRD+ status, ASCT |
| Study . | Number of patients and characteristics . | Chemotherapy . | MRD technique and limit of detection . | MRD-related outcomes . |
|---|---|---|---|---|
| MRD for evaluating treatment efficacy | ||||
| PETHEMA/GEM2012 trial randomized phase 3 study NCT01916252 Paiva et al26 | N = 458 TE NDMM | Induction VRd (×6) ASCT Consolidation VRd (×2) | NGF median, 3 × 10−6 | MRD– status after induction, 28%
|
| UK OPTIMUM /MUKnine trial phase 2 study NCT03188172 Kaiser et al27 | N = 95 ultrahigh-risk NDMM | Induction D-CVRd (×6) ASCT Consolidation D-CVRd (×6) D-VR (×12) Maintenance D-R | MFC, 10−5 | MRD status on day +100 after ASCT: MRD–, 64% MRD+, 14% MRD not evaluable, 22% |
| GMMG-HD7 study randomized phase - study NCT03617731 Goldschmidt et al28 | N = 662 TE NDMM | Induction: VRd ± I | NGF, 10−5 | After induction: MRD– status:
|
| MRD for comparing the efficacy of different treatment approaches | ||||
| CASSIOPEIA randomized phase 3 study NCT02541383 Moreau et al29 | N = 1085 TE NDMM | Induction D-VTd vs VTd (×4) ASCT Consolidation VTd vs VTd (×2) Maintenance D vs observation | MFC, 10−5 | Day +100 after ASCT: MRD– status:
|
| BENEFIT: IFM2020-05 randomized phase 3 study NCT04751877 Leleu et al30 | N = 270 TIE, nonfrail NDMM | Isa-VRD vs Isa-Rd | NGS, 10−5 | Primary end point: MRD at 18 mo (ongoing) |
| EMN28/CARTITUDE-6 randomized phase 3 study NCT0525708331 | N = 750 TE NDMM | cilta-cel vs ASCT | NGS, 10−5 | Dual primary end points: PFS and sustained MRD |
| MRD for adapting therapy | ||||
| MIDAS randomized phase 3 study NCT04934475 Moreau32 | N = 716 TE NDMM | Induction Isa-KRd (×6) Standard risk (NGS, <10−5): arm A; 6 additional cycles of Isa-KRd vs arm B: ASCT followed by 2 cycles of Isa-KRd; High risk (NGS, >10−5): arm C: ASCT followed by 2 cycles of Isa-KRd vs arm D: tandem ASCT | NGS, 10−5 | Randomization based on MRD assessment after induction |
| MRD for adapting maintenance therapy and duration | ||||
| EMN017/MMY3014 (Perseus) randomized phase 3 NCT0371060333 | N = 690 TE NDMM | Induction: D-VRd vs VRd (×4) ASCT Induction: D-VRd vs VRd (×2) Maintenance DR vs R until progression | NGS, 10−5 | D-VRD arm : 12 mo sustained MRD and ≥ 2 y maintenance: D interruption |
| GEM2014 trial randomized phase 3 study NCT02406144 Rosinol et al34 | N = 316 TE NDMM | Maintenance ixazomib-Rd vs Rd for 2 y | NGF, 3 × 10−6 | At 2 y. MRD– status: maintenance interruption MRD+ status: pursue Rd alone for 3 more years |
| MRD for introduction of ERI | ||||
| REMNANT trial randomized phase 2/3 study NCT04513639 Askeland et al35 | N = 176 TE NDMM | Induction VRd (×4) ASCT (×1 or 2) Consolidation VRd (×2) | NGF, 10−5 | For patients with MRD– status: randomization
|
| GEM-TECTAL trial phase 2 study NCT0584961036 | N = 30: high risk, R-ISS-III, TE, and fit TIE NDMM | Induction D-VRd (×4) Intensification: D-teclistamab (×6) | NGF, 10−6 | MRD assessment after intensification: MRD– status: D-teclistamab 2y. MRD+ status or not in CR: D – talquetamab, and after 6 cycles: MRD– status, pursue for 2 y; MRD+ status, ASCT |
C, cyclophosphamide; cilta-cel, ciltacabtagene autoleucel; d, dexamethasone; D, daratumumab; I, isatuximab; MFC, multiparameter flow cytometry; OR, odds ratio; R, lenalidomide; TE, transplantation eligible; TIE, transplantation ineligible; V, bortezomib.