List of studies reporting rates of MRD negativity in patients with persistent M protein
| Study . | Method . | Sensitivity . | Patients with undetectable MRD . | Outcome . | Reference . | |
|---|---|---|---|---|---|---|
| CR (%) . | Less than CR (%) . | |||||
| GEM2000 | Flow cytometry | 10−4 | 94/125 (75) | 31/125 (25) | Median PFS, 71 vs 65 mo | 26 |
| GEM2005MAS65 | Flow cytometry | 10−4 | 24/31 (77) | 7/31 (23) | Median PFS not reached in either∗ | 28 |
| PETHEMA/GEM† | Flow cytometry | 10−4 to 10−5 | 177/259 (68) | 82/259 (32) | Median PFS, 63 vs 62 mo | 4 |
| MRC Myeloma IX | Flow cytometry | 10−4 | 183/246 (74) | 63/246 (26) | Not reported‡ | 27 |
| NCT00861250 | Flow cytometry | 6 × 10−5 | 56/91 (61.5) | 35/91 (38.5) | Not reported | 31 |
| NCT01402284 | Flow cytometry | 10−5 | 29/34 (85) | 5/34 (25) | Not reported | 36 |
| NCT01816971 | Flow cytometry | 10−4 to 10−5 | 34/45 (75.5) | 11/45 (24.5) | Not reported | 18 |
| GEM2012MENOS65 | NGF | 3 × 10−6 | 182/205 (89) | 23/205 (11) | 4-y rate, 87% vs 78.5%; P = .35 | 40 |
| GMMG-HD6 | NGF | 6 × 10−6 | 37/54 (68.5) | 17/54 (31.5) | Not reported | 34 |
| Tschautscher et al | NGF | 10−5 to 2 × 10−6 | 116/204 (57) | 88/204 (43) | Median PFS not reached in either§ | 39 |
| GEM2000 | F-PCR | Not reported | 19/26 (73) | 7/26 (27) | Not reported | 29 |
| GEM2000 | ASO qRT-PCR | 10−5 | 6/7 (86) | 1/7 (14) | Not reported | 30 |
| NCT00861250 | ASO qRT-PCR | 4 × 10−6 | 37/60 (62) | 23/60 (38) | Not reported | 31 |
| PETHEMA/GEM‖ | NGS | 10−5 | 26/30 (87) | 4/30 (13) | Not reported | 32 |
| NCT01402284 | NGS | Not reported | 22/23 (96) | 1/23 (4) | Not reported | 36 |
| IFM-2009 | NGS | 10−6 | 54/90 (60) | 36/90 (40) | Not reported | 33 |
| GMMG-HD6 | NGS | 2 × 10−6 | 37/60 (62) | 23/60 (38) | Not reported | 34 |
| Takamatsu et al | NGS | 10−6 | 24/26 (92) | 2/26 (8) | Not reported | 35 |
| NCT01816971 | NGS | 10−4 to 10−6 | 35/38 (92) | 3/38 (8) | Not reported | 18 |
| Hillengass et al | MRI | Not reported | 3/23 (13) | 20/23 (87) | Not reported | 37 |
| NCT01816971 | PET/CT | Not reported | 20/28 (71) | 8/28 (29) | Not reported | 18 |
| Study . | Method . | Sensitivity . | Patients with undetectable MRD . | Outcome . | Reference . | |
|---|---|---|---|---|---|---|
| CR (%) . | Less than CR (%) . | |||||
| GEM2000 | Flow cytometry | 10−4 | 94/125 (75) | 31/125 (25) | Median PFS, 71 vs 65 mo | 26 |
| GEM2005MAS65 | Flow cytometry | 10−4 | 24/31 (77) | 7/31 (23) | Median PFS not reached in either∗ | 28 |
| PETHEMA/GEM† | Flow cytometry | 10−4 to 10−5 | 177/259 (68) | 82/259 (32) | Median PFS, 63 vs 62 mo | 4 |
| MRC Myeloma IX | Flow cytometry | 10−4 | 183/246 (74) | 63/246 (26) | Not reported‡ | 27 |
| NCT00861250 | Flow cytometry | 6 × 10−5 | 56/91 (61.5) | 35/91 (38.5) | Not reported | 31 |
| NCT01402284 | Flow cytometry | 10−5 | 29/34 (85) | 5/34 (25) | Not reported | 36 |
| NCT01816971 | Flow cytometry | 10−4 to 10−5 | 34/45 (75.5) | 11/45 (24.5) | Not reported | 18 |
| GEM2012MENOS65 | NGF | 3 × 10−6 | 182/205 (89) | 23/205 (11) | 4-y rate, 87% vs 78.5%; P = .35 | 40 |
| GMMG-HD6 | NGF | 6 × 10−6 | 37/54 (68.5) | 17/54 (31.5) | Not reported | 34 |
| Tschautscher et al | NGF | 10−5 to 2 × 10−6 | 116/204 (57) | 88/204 (43) | Median PFS not reached in either§ | 39 |
| GEM2000 | F-PCR | Not reported | 19/26 (73) | 7/26 (27) | Not reported | 29 |
| GEM2000 | ASO qRT-PCR | 10−5 | 6/7 (86) | 1/7 (14) | Not reported | 30 |
| NCT00861250 | ASO qRT-PCR | 4 × 10−6 | 37/60 (62) | 23/60 (38) | Not reported | 31 |
| PETHEMA/GEM‖ | NGS | 10−5 | 26/30 (87) | 4/30 (13) | Not reported | 32 |
| NCT01402284 | NGS | Not reported | 22/23 (96) | 1/23 (4) | Not reported | 36 |
| IFM-2009 | NGS | 10−6 | 54/90 (60) | 36/90 (40) | Not reported | 33 |
| GMMG-HD6 | NGS | 2 × 10−6 | 37/60 (62) | 23/60 (38) | Not reported | 34 |
| Takamatsu et al | NGS | 10−6 | 24/26 (92) | 2/26 (8) | Not reported | 35 |
| NCT01816971 | NGS | 10−4 to 10−6 | 35/38 (92) | 3/38 (8) | Not reported | 18 |
| Hillengass et al | MRI | Not reported | 3/23 (13) | 20/23 (87) | Not reported | 37 |
| NCT01816971 | PET/CT | Not reported | 20/28 (71) | 8/28 (29) | Not reported | 18 |
ASO, allele-specific oligonucleotide; CT, computed tomography; F-PCR, fluorescence-based PCR; MRI, magnetic resonance imaging; PET, positron emission tomography; qRT-PCR, quantitative real-time PCR.
The outcome comparison reported was between MRD-negative patients in stringent CR vs no stringent CR.
Pooled analysis of the GEM2000, GEM2005MENOS65, and GEM2010MAS65 clinical trials.
Although not reported, it seems that patients with undetectable MRD and less than CR had inferior outcomes when compared with those in CR.
At 1 y, risk of progressive disease was 20% in the CR group compared with 40% in the non-CR group (P = .004 per Wilcoxon test).
Pooled analysis of the GEM2000, GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 clinical trials.