Table 2.
NDMM patients treated with novel agents: latest selected studies with MRD analysis.
| Reference | MRD Technique (Sensitivity) | Study Population and Treatment | Time Point Assessment | MRD Rate | Survival Outcomes |
|---|---|---|---|---|---|
| Paiva B. et al. 2016 [51] | MFC (10−5) | NTE NDMM pts (N = 162) Sequential or alternating VMP/Rd cycles |
With response ≥VGPR after 9 or 18 sequential or alternating VMP/Rd cycles | Sequential arm: 9-cycles: 20%; 18-cycles: 46% Alternating arm: 9-cycles: 19%; 18-cycles: 33% |
Median TTP: NR vs. 15 mo |
| Oliva S. et al. 2017 [52] | MFC (10−5) | TE NDMM pts (N = 316) VCd induction, VMP vs. ASCT intensification, VRd vs. no consolidation followed by lenalidomide maintenance |
With response ≥VGPR; pre and during maintenance | Post consolidation: 76% |
3-year PFS: 77% vs. 50% |
| Ocio E.M. et al. 2018 [53] | NGF (10−5) and NGS (10−5) |
NTE NDMM pts (N = 16) Isa-VRd induction followed by Isa-Rd maintenance |
Longitudinal | NGF 44% (18% at 10−6) NGS 50% (33% at 10−6) |
NA |
| Zimmerman T. et al. 2018 [54] | MFC (10−4−10−5) and NGS (10−6) | TE NDMM pts (N = 76) 4 cycles of KRd induction-ASCT-4 cycles of KRd consolidation and 10 cycles of KRd extended consolidation |
Longitudinal | MFC: post consolidation (cycle 8): 82%; post extended consolidation (cycle 18): 90% NGS: post consolidation (cycle 8): 66%; post extended consolidation (cycle 18): 71% |
According to cycle 8, MRD status by MFC and/or NGS: 2-year PFS 100% vs. 93% |
| Perrot A. et al. 2018 [17] | NGS (10−6) | TE NDMM pts (N = 509) 8 VRd cycles or 3 VRd + ASCT + 2 VRd cycles followed by lenalidomide maintenance |
Pre or post maintenance | VRd alone arm: 20% ASCT arm: 30% |
Median PFS: NR vs. 29 months |
| Mateos M.V. et al. 2019 [2,3,55] | NGS (10−5) | NTE NDMM pts (N = 706) - Dara-VMp vs.- VMp arm |
Longitudinal | Dara-VMp arm: 28% VMp arm: 7% |
NA |
| Facon T. et al. 2019 [1]. | NGS (10−5) | NTE NDMM pts (N = 737) - Dara-Rd arm - Rd arm |
Longitudinal | Dara-Rd arm: 24.2% Rd arm: 7.3% |
NA |
| Gay F. et al. 2019 [56] | MFC (10−5) | TE NDMM pts (N = 474) - KCd-ASCT-KCd (arm A, 159); - KRd-ASCT-KRd (arm B, 158); - 12 cycles of KRd (arm C, 157). |
Longitudinal | Arm A: 42% Arm B: 58% Arm C: 54% |
NA |
| Avet-Loiseau H. et al. 2019 [57] | MFC (10−5) and NGS (10−6) | TE NDMM pts (N = 1085) - Dara-VTd-ASCT-Dara-VTd - or VTd-ASCT-VTd |
Post induction and post consolidation | Post induction MFC: Dara-VTd arm: 35%; VTd arm: 23% Post consolidation MFC: Dara-VTd arm: 64%; VTd arm: 44% Post consolidation NGS in evaluable patients: Dara-VTd arm: 39%; VTd arm 23% |
NA |
| Voorhees P.M. et al. 2019 [4,5,58] | NGS (10−5) | TE NDMM pts (N = 104) Dara-VRd induction, ASCT and Dara-VRd consolidation |
Longitudinal | Post induction: 15% Post consolidation: 44% |
NA |
| Paiva B. et al. 2020 [23] | MFC (10−4, 10−6) | TE NDMM pts (N = 458) 6 VRd induction cycles, ASCT and 2 VRd consolidation cycles |
CR patients, after induction, + 100 after ASCT, after consolidation | Post induction: 28% Post ASCT: 42% Post consolidation: 45% |
PFS: 82% MRD neg vs. 50% MRD pos; 36 mo OS: 96% MRD neg vs. 88% MRD pos |
| Costa L.J. et al. 2019 [59] | NGS (<10−5) | TE NDMM pts (N = 81) Dara-KRd induction, ASCT, Dara-KRd consolidation |
Longitudinal | Post induction: 40% Post ASCT: 73% Post consolidation: 82% |
NA |
| Landgren O. et al. 2019 [60] | NGS (10−5) | TE and NTE NDMM pts (N = 24) 8 Dara-KRd cycles |
After 8 cycles | 75% | NA |
Abbreviations. NDMM, newly diagnosed multiple myeloma; MRD, minimal residual disease; MFC, multiparameter flow cytometry; NGF, next-generation flow; NGS, next-generation sequencing; NTE; non-transplant-eligible; TE, transplant-eligible; N, number; V, bortezomib; M, melphalan; P, p, prednisone; R, lenalidomide; d, dexamethasone; Isa, isatuximab; K, carfilzomib; ASCT, autologous stem-cell transplantation; Dara, daratumumab; M, melphalan; C, cyclophosphamide; T, thalidomide; VGPR, very good partial response; CR; complete remission; TTP, time to progression; PFS, progression-free survival; NR, not reached; NA, not available; OS, overall survival; Neg, negative; pos, positive; mo, months.