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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

From: Measurable residual disease in multiple myeloma: ready for clinical practice?

StudyTreatmentOutcomeMRD assessmentMRD-negative rate
Transplant-eligible
 IFM2009 (NCT01191060) [22, 34]HDT vs RVDHDT: median PFS 50m
RVD: median PFS 36m
NGS (10−6)aHDT 30%
RVD 20%
 CASSIOPEIA (NCT02541383) [10]D-VTd vs VTdD-VTD: 18m PFS 93%
VTD: 18m PFS 85%
NGF (10−5)D-VTD 64%
VTD 44%
Transplant-ineligible
 ALCYONE (NCT02195479) [25]D-VMP vs VMPD-VMP: median PFS NR
VMP: median PFS 18.1m
NGS (10−5)D-VMP 22.3%
VMP 6.2%
 CLARION (NCT01818752) [27]KMP vs VMPKMP: median PFS 22.3m
VMP: median PFS 22.1m
NGF (10−6)KMP 15.7%
VMP 15.5%
 MAIA (NCT02252172) [26]DRd vs RdDRd: median PFS NR
Rd: median PFS 31.9m
NGS (10−5)DRd 24.2%
Rd 7.3%
Relapse/refractory
 POLLUX (NCT02076009) [30]DRd vs RdDRd: median PFS NR
Rd: median PFS 17.5m
NGS (10−5)DRd 22.4%
Rd 4.6%
 CASTOR (NCT02136134) [29]DVd vs VdDVd: median PFS 16.7m
Vd: median PFS 7.1m
NGS (10−5)DVd 11.6%
Vd 2.4%
  1. 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
  2. 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.