Table 2.
Prospective randomized clinical trials with MRD assessment using next-generation techniques. These studies were selected based on reported effect of treatment randomization in patients’ outcome and MRD negativity rates. Overall, whenever significant differences in MRD rates are observed, these predicted significant differences in outcome
| Study | Treatment | Outcome | MRD assessment | MRD-negative rate |
|---|---|---|---|---|
| Transplant-eligible | ||||
| IFM2009 (NCT01191060) [22, 34] | HDT vs RVD |
HDT: median PFS 50m RVD: median PFS 36m |
NGS (10−6)a |
HDT 30% RVD 20% |
| CASSIOPEIA (NCT02541383) [10] | D-VTd vs VTd |
D-VTD: 18m PFS 93% VTD: 18m PFS 85% |
NGF (10−5) |
D-VTD 64% VTD 44% |
| Transplant-ineligible | ||||
| ALCYONE (NCT02195479) [25] | D-VMP vs VMP |
D-VMP: median PFS NR VMP: median PFS 18.1m |
NGS (10−5) |
D-VMP 22.3% VMP 6.2% |
| CLARION (NCT01818752) [27] | KMP vs VMP |
KMP: median PFS 22.3m VMP: median PFS 22.1m |
NGF (10−6) |
KMP 15.7% VMP 15.5% |
| MAIA (NCT02252172) [26] | DRd vs Rd |
DRd: median PFS NR Rd: median PFS 31.9m |
NGS (10−5) |
DRd 24.2% Rd 7.3% |
| Relapse/refractory | ||||
| POLLUX (NCT02076009) [30] | DRd vs Rd |
DRd: median PFS NR Rd: median PFS 17.5m |
NGS (10−5) |
DRd 22.4% Rd 4.6% |
| CASTOR (NCT02136134) [29] | DVd vs Vd |
DVd: median PFS 16.7m Vd: median PFS 7.1m |
NGS (10−5) |
DVd 11.6% Vd 2.4% |
MRD measurable residual disease, HDT high-dose therapy, D Daratumumab, V Bortezomib, T Thalidomide, d Dexamethasone, M Melphalan, P Prednisone, K Carfilzomib, R Lenalidomide, PFS progression-free survival, m months, NR not reached, NGF next-generation flow, NGS next-generation sequencing
aThis study also reported MRD rates based on a 7-color flow cytometry assay that, similarly to the results obtained by NGS, showed significant differences between the HDT vs RVD arm.