Selected studies of MRD assessment in myeloma
| Study* . | Treatment arms . | Test method . | % MRD negative . | Outcomes (MRD-negative vs MRD-positive) . |
|---|---|---|---|---|
| Paiva et al.10 | Six alternating cycles of VBMCP and VBAD, followed by ASCT (n = 577) | Four-color flow cytometry | 42% | Median PFS 71 mo vs 37 mo (P < .001) |
| Median OS not reached vs 89 mo (P = .002) | ||||
| Paiva et al11 | Six cycles of VMP or VTP (n = 102) | Four-color flow cytometry | 30% | Median PFS not reached vs 35 mo (P = .02) |
| Median OS not significantly different | ||||
| Korthals et al.12 | Idarubicin or dexamethasone plus ASCT (n = 53) | ASO-PCR | 49% | Median EFS 35 mo vs 20 mo (P = .001) |
| Median OS 70 mo vs 45 mo (P = .04) | ||||
| Paiva et al.13 | Conv chemo or TD or VTD and ASCT (n = 241) | Four-color flow cytometry | 74% of BM CR | PFS 86% vs 58% at 3 y (P < .001) |
| OS 94% vs 80% at 3 y (P = .001) | ||||
| Rawstron et al.14 | CVAD or CTD plus ASCT (n = 378) | Six-color flow cytometry | 62% | Median PFS 28.6 mo vs 15.5 mo (P < .001) |
| Median OS 80.6 mo vs 59 mo (P = .018) | ||||
| Rawstron et al.14 | MP vs CTD (n = 245) | Six-color flow cytometry | 15% | Median PFS 10.5 mo vs 7.4 mo (P = .1) |
| Martinez-Lopez et al.15 | VBMC or VBAD induction therapy plus ASCT or 6 cycles of VMP or VTP (n = 133) | NGS | Median TTP 80 mo vs 31 mo (P < .0001) | |
| Median OS not reached versus 81 mo (P = .02) | ||||
| Puig et al.16 | VBMC or VBAD induction therapy plus ASCT or 6 cycles of VMP or VTP (n = 170) | ASO-PCR | 47% | VBMCP or VBAD induction therapy plus HDT–ASCT: median PFS 54 mo vs 27 mo (P = .001); OS not significantly different 6 cycles of VMP or VTP: median PFS not reached versus 31 mo (P = .029); OS not significantly different |
| Roussel et al.17 | VRD plus ASCT plus VRD plus Len (n = 31) | Seven-color flow cytometry | 68% | PFS 100% vs 30% at 3 y |
| Ferrero et al.18 | VTD plus ASCT (n = 39) | ASO-PCR | — | OS 72% vs 48% at 8 y (P = .0041) |
| Korde et al.19 | KRD (n = 45) | NGS | — | PFS 100% vs 79% at 12 mo (P < .001) |
| Ludwig et al.20 | VTD ± C (n = 42) | Four-color flow cytometry | 80% of BM CR | Median PFS not reached vs 38.6 mo (P = .085) |
| Avet-Loiseau et al21 | VD or RD ± Daratumumab (n = 474, n = 557) | NGS | 0.8%–9.8% | MRD-negative patients experienced fewer progression events than MRD-positive patients |
| Oliva et al.22 | Induction plus VMP, CRD, or ASCT, followed by Len (n = 105) | ASO-PCR | 45% | Median PFS not reached vs 48.8 mo (P = .01) |
| Paiva et al.23 | Alternating VMP plus RD (n = 162) | NGF | 34% | Median TTP not reached vs 15 mo OS 70% vs 55% at 3 y |
| de Tute et al.24 | CTDa or RCDa = /− Len (n = 297) | Six-color flow cytometry | 13.8% (10.8%–16.0%) | Median PFS 34 mo vs 18 mo (P < .0001) |
| Attal et al.25 | VRD ± ASCT plus VRD plus Len (n = 543) | Seven-color flow cytometry | 65%–79% | MRD-negative patients experienced longer PFS than MRD-positive patients (adjusted HR 0.30 P < .001) |
| MRD-negative patients experienced longer OS than MRD-positive patients (adjusted HR 0.34 P < .001) |
| Study* . | Treatment arms . | Test method . | % MRD negative . | Outcomes (MRD-negative vs MRD-positive) . |
|---|---|---|---|---|
| Paiva et al.10 | Six alternating cycles of VBMCP and VBAD, followed by ASCT (n = 577) | Four-color flow cytometry | 42% | Median PFS 71 mo vs 37 mo (P < .001) |
| Median OS not reached vs 89 mo (P = .002) | ||||
| Paiva et al11 | Six cycles of VMP or VTP (n = 102) | Four-color flow cytometry | 30% | Median PFS not reached vs 35 mo (P = .02) |
| Median OS not significantly different | ||||
| Korthals et al.12 | Idarubicin or dexamethasone plus ASCT (n = 53) | ASO-PCR | 49% | Median EFS 35 mo vs 20 mo (P = .001) |
| Median OS 70 mo vs 45 mo (P = .04) | ||||
| Paiva et al.13 | Conv chemo or TD or VTD and ASCT (n = 241) | Four-color flow cytometry | 74% of BM CR | PFS 86% vs 58% at 3 y (P < .001) |
| OS 94% vs 80% at 3 y (P = .001) | ||||
| Rawstron et al.14 | CVAD or CTD plus ASCT (n = 378) | Six-color flow cytometry | 62% | Median PFS 28.6 mo vs 15.5 mo (P < .001) |
| Median OS 80.6 mo vs 59 mo (P = .018) | ||||
| Rawstron et al.14 | MP vs CTD (n = 245) | Six-color flow cytometry | 15% | Median PFS 10.5 mo vs 7.4 mo (P = .1) |
| Martinez-Lopez et al.15 | VBMC or VBAD induction therapy plus ASCT or 6 cycles of VMP or VTP (n = 133) | NGS | Median TTP 80 mo vs 31 mo (P < .0001) | |
| Median OS not reached versus 81 mo (P = .02) | ||||
| Puig et al.16 | VBMC or VBAD induction therapy plus ASCT or 6 cycles of VMP or VTP (n = 170) | ASO-PCR | 47% | VBMCP or VBAD induction therapy plus HDT–ASCT: median PFS 54 mo vs 27 mo (P = .001); OS not significantly different 6 cycles of VMP or VTP: median PFS not reached versus 31 mo (P = .029); OS not significantly different |
| Roussel et al.17 | VRD plus ASCT plus VRD plus Len (n = 31) | Seven-color flow cytometry | 68% | PFS 100% vs 30% at 3 y |
| Ferrero et al.18 | VTD plus ASCT (n = 39) | ASO-PCR | — | OS 72% vs 48% at 8 y (P = .0041) |
| Korde et al.19 | KRD (n = 45) | NGS | — | PFS 100% vs 79% at 12 mo (P < .001) |
| Ludwig et al.20 | VTD ± C (n = 42) | Four-color flow cytometry | 80% of BM CR | Median PFS not reached vs 38.6 mo (P = .085) |
| Avet-Loiseau et al21 | VD or RD ± Daratumumab (n = 474, n = 557) | NGS | 0.8%–9.8% | MRD-negative patients experienced fewer progression events than MRD-positive patients |
| Oliva et al.22 | Induction plus VMP, CRD, or ASCT, followed by Len (n = 105) | ASO-PCR | 45% | Median PFS not reached vs 48.8 mo (P = .01) |
| Paiva et al.23 | Alternating VMP plus RD (n = 162) | NGF | 34% | Median TTP not reached vs 15 mo OS 70% vs 55% at 3 y |
| de Tute et al.24 | CTDa or RCDa = /− Len (n = 297) | Six-color flow cytometry | 13.8% (10.8%–16.0%) | Median PFS 34 mo vs 18 mo (P < .0001) |
| Attal et al.25 | VRD ± ASCT plus VRD plus Len (n = 543) | Seven-color flow cytometry | 65%–79% | MRD-negative patients experienced longer PFS than MRD-positive patients (adjusted HR 0.30 P < .001) |
| MRD-negative patients experienced longer OS than MRD-positive patients (adjusted HR 0.34 P < .001) |
Abbreviations: ASCT, high-dose (chemo) therapy and autologous stem-cell transplantation; ASO-PCR, allele-specific oligonucleotide PCR; BM, bone marrow; CTD, cyclophosphamide, thalidomide, and dexamethasone; CVAD, cyclophosphamide, vincristine, Adriamycin, and dexamethasone; EFS, event-free survival; HR, hazard ratio; KRD, kyprolis revlimid, dexamethasone; Len, lenalidomide; MP, melphalan and prednisolone; MRD, minimal residual disease; NGF, next-generation flow cytometry; NGS, next-generation sequencing; OS, overall survival; PFS, progression-free survival; RCDa, revlimid, cyclophosphamide and dexamethasone (attenuated); TD, thalidomide and dexamethasone; TTP, time to progression; VRD, velcade revlimid, dexamethasone; VBAD, vincristine, carmustine, adriamycin, and dexamethasone; VBMCP, vincristine, carmustine, melphalan, cyclophosphamide, and prednisone; VMP, bortezomib, melphalan, and prednisone; VTD, velcade, thalidomide, and dexamethasone; VTP, bortezomib, thalidomide, and prednisone.
I apologize that I am only able to mention a small number of the studies concerning MRD in myeloma. I would like to acknowledge the work of all of my colleagues who have contributed to the knowledge of MRD in myeloma.