Table 1 The detection efficiency and sensitivity of different methods in liquid biopsy
Method | Detection efficiency and sensitivity | Reference |
|---|---|---|
Wright–Giemsa-stained blood smears | CMMCs were detected in approximately 14.1%–20.8% of patients with NDMM at diagnosis | |
Slide-based immunofluorescence | Sensitivity: 0.01% CMMCs were detected in 19.4%, 25%, and 80% of patients with MGUS, SMM, and NDMM, respectively | |
MFC (2-color: CD45 and CD38) | Sensitivity: 0.01% CMMCs were detected in 20%, 40%, 73%–83.6%, and 38.6% of patients with MGUS, SMM, NDMM at diagnosis, and MM before ASCT, respectively | |
MFC (5-color: CD38, CD138, CD45, CD19, and CD56) | Sensitivity: 0.01% CMMCs were detected in approximately 69.2%–74.1%, 60.5%, 0%, and 14% of patients with NDMM at diagnosis, in PR, in CR, and at relapse, respectively | |
MFC (6-color: CD38, CD138, CD45, CD19, cytoplasmic κ, and λ light chains) | Sensitivity: 20 cells/150,000 events (0.013%) CMMCs were detected in 24%, approximately 51.4%–67%, approximately 19.3%–19.4%, and 62/145 of patients with SMM, NDMM before therapy, MM before ASCT, and MM at relapse, respectively | |
MFC (7-color: CD38, CD138, CD45, CD19, CD56, cytoplasmic κ, and λ light chains) | Sensitivity: 0.01% CMMCs were detected in 60.1% and 18.8% of patients with NDMM at diagnosis and MM before ASCT, respectively | |
2 tubes/MFC (7-color: CD38, CD138, CD45, CD19, CD56, cytoplasmic κ, and λ light chains) | Sensitivity: approximately 0.004%–0.0001% CMMCs were detected in 119/191 (approximately 67%) of patients with NDMM at diagnosis | |
Magnetic cell sorting (MACS) (CD38 or CD138) combined with MFC (5-color: CD38, CD138, CD45, CD19, and CD56) | Sensitivity: 0.001% CMMCs were detected in 87.2%, approximately 83.7%–86%, approximately 5%–10%, and 85% of patients with NDMM at diagnosis, in PR, in CR, and at relapse, respectively | [23] |
MACS (CD138) combined with MFC (6-color: CD38, CD138, CD45, CD19, CD56, and CD117) | CMMCs were detected in 55.5% and 28.6% of patients with MM with EM at diagnosis and NDMM without EM at diagnosis, respectively | [35] |
MACS (CD138) combined with MFC (7-color: CD45, CD19, CD81, CD27, CD117, CD56, and CD200) | CMMCs were detected in 83.3% and 9.9% of patients with NDMM/MM at relapse and MM who achieved CR, respectively | [36] |
NGF (2-tube/8-color) | Sensitivity: 0.0001% CMMCs were detected in approximately 92%–100%, 100%, 59%, 25%, 18%, 17%, and 100% of patients with NDMM at diagnosis, SMM, MGUS, macro focal MM, solitary plasmacytoma, MM who achieved CR/sCR, and relapsed/refractory multiple myeloma (RRMM), respectively | |
CellSearch platform | CMMCs were detected in 98%, 93.7%, and approximately 56%–86% of patients with NDMM at baseline, intermediate/high-risk SMM, and MGUS, respectively | [39] |
Epic platform | Sensitivity: one MM cell in 3*106 WBCs | [40] |
CD138-coated microfluidic device (Herringbone-shaped) | Sensitivity: < 10 CMMCs/mL using 1-mL sample | [41] |
CD138-coated microfluidic device (Sinusoidal-shaped) | CMMCs were detected in 78% of patients with MGUS and 100% of those with SMM and MM | [42] |
ASO-PCR of IGH rearrangements | Sensitivity: 0.001% CMMCs were detected in 13/16, 6/8, and 13/15 of patients with MGUS, SMM, and active MM, respectively | [4] |
Real-time quantitative PCR of IGH rearrangements | Sensitivity: approximately 0.01%–0.001% CMMCs were detected in 67%, 43%, 25%, and 73% of patients with NDMM at diagnosis, NDMM before HDT for ASCT, NDMM 3 months after HDT, and RRMM at the time of relapse, respectively | |
LymphoSIGHT assay of IGH and IGK rearrangements | Sensitivity: well below 0.0001% 1. CMMCs were detected in 78% of patients with MM using DNA assay and 96% of patients with MM using DNA and RNA assays 2. ctDNA was detected in 83% of patients with MM using DNA assay 3. Tumor clones were detected in 98% of patients with MM using the combination of CMMCs and ctDNA | [44] |
Ion Torrent of IGH rearrangements | Sensitivity: 0.001% MM clones in cfDNA were detected in 100% of patients with MM at relapse | [12] |
NGS of IGK and IGL rearrangements | MM clones in cfDNA were detected in 71.4% of patients with NDMM/MM at relapse and 22.2% of samples from MM who achieved CR. All ctDNA-detectable CR samples were from a patient with nonsecretory MM | [36] |
NGS of IGH, IGK, and IGL rearrangements | CMMCs were detected in 71% of patients with MM at baseline. MM clones in cfDNA were detected in 100% of patients with MM at baseline. MM clones in CMMCs and/or cfDNA were detected in 91% and 41% of patients with MM with stable or progressive disease and MM with PR or better, respectively | [45] |
ULP-WGS | Lower limit: TF ≥ 3% In NDMM/RRMM, ≥ 3% TF was detected in 76% cfDNA samples and 100% CMMC samples; ≥ 10% TF was detected in approximately 24%–32% cfDNA samples and in 31% CMMC samples In MGUS/SMM/NDMM/RRMM, ≥ 3% TF was detected in 58% cfDNA samples and 96% CMMC samples; ≥ 10% TF was detected in 17% cfDNA samples and 21% CMMC samples | |
LP-WGS | Lower limit: TF ≥ 5%  ≥ 5% TF was detected in 62% of cfDNA samples from patients with RRMM, in 75% of cfDNA samples from patients with NDMM, and in none of cfDNA samples from patients with MM post-treatment | [49] |