Clinical significance of posttreatment MRD analysis as determined by a method with sensitivity of at least 10−4, after first-line combination chemotherapy or chemoimmunotherapy
| Study . | Treatment . | No. of patients with MRD testing, (% MRD negative) . | MRD threshold, sample source, method . | PFS . | P value . | Overall survival . | P value . |
|---|---|---|---|---|---|---|---|
| Bosch et al 20083 | FCM | 18 (41%) | 10−4, FLC BM | MRD-positive CR < MRD-negative CR | .2 | Not reported | NA |
| Lamanna et al 200943 | F→C→R | 23 (52%) | Nested ASO IGHV PCR 10−5 | 35 months vs NR | .007 | Not reported | NA |
| Maloum et al 200944 | FC | 21 (64%) | 10−4, FLC PB | DFS, median/HR not reported | <.001 | No difference | NS |
| Bottcher et al 201210 | FC or FCR | 290*† | 10−2 and 10−4, FLC PB | 15, 41, and 69 months for ≥10−2, ≥10−4 to <10−2, and <10−4, respectively‡ | <.001 | Significantly inferior for ≥10−2 vs <10−2 | <.001 |
| Fischer et al 201246 | BR | 45 (58%) | 10−2 and 10−4, FLC PB | 12 months, 32 months, and NR for ≥10−2, ≥10−4 to <10−2, and <10−4, respectively | <.001 | 23.2 months for ≥10−2 vs NR for <10−2 | Not reported |
| Abrisqueta et al 201347 | R+FCM | 63 (56%) | 10−4, FLC BM | 4 years; 86% vs 60%‡ | .03 | Not reported | Not reported |
| Strati et al 201448 | FCR | 161 (43%) | 10−4, FLC BM | HR 0.1 (median NR)‡ | .03 | HR 0.6 (median NR)‡ | .02 |
| Goede et al 201415 | Obinutuzumab + Clb | 133 (20%) in BM, 231 (38%) in PB | 10−4, FLC PB/BM | 19.4 months vs NR†‡ | <.001 | Not reported | NA |
| Kwok et al 201445 | Predominantly F-based combinations | 57 first-line (42%) | 10−4, FLC BM | 5 years; 81% vs 16%‡ | <.001 | 10 years; 53% vs 24%‡ | <.001 |
| Study . | Treatment . | No. of patients with MRD testing, (% MRD negative) . | MRD threshold, sample source, method . | PFS . | P value . | Overall survival . | P value . |
|---|---|---|---|---|---|---|---|
| Bosch et al 20083 | FCM | 18 (41%) | 10−4, FLC BM | MRD-positive CR < MRD-negative CR | .2 | Not reported | NA |
| Lamanna et al 200943 | F→C→R | 23 (52%) | Nested ASO IGHV PCR 10−5 | 35 months vs NR | .007 | Not reported | NA |
| Maloum et al 200944 | FC | 21 (64%) | 10−4, FLC PB | DFS, median/HR not reported | <.001 | No difference | NS |
| Bottcher et al 201210 | FC or FCR | 290*† | 10−2 and 10−4, FLC PB | 15, 41, and 69 months for ≥10−2, ≥10−4 to <10−2, and <10−4, respectively‡ | <.001 | Significantly inferior for ≥10−2 vs <10−2 | <.001 |
| Fischer et al 201246 | BR | 45 (58%) | 10−2 and 10−4, FLC PB | 12 months, 32 months, and NR for ≥10−2, ≥10−4 to <10−2, and <10−4, respectively | <.001 | 23.2 months for ≥10−2 vs NR for <10−2 | Not reported |
| Abrisqueta et al 201347 | R+FCM | 63 (56%) | 10−4, FLC BM | 4 years; 86% vs 60%‡ | .03 | Not reported | Not reported |
| Strati et al 201448 | FCR | 161 (43%) | 10−4, FLC BM | HR 0.1 (median NR)‡ | .03 | HR 0.6 (median NR)‡ | .02 |
| Goede et al 201415 | Obinutuzumab + Clb | 133 (20%) in BM, 231 (38%) in PB | 10−4, FLC PB/BM | 19.4 months vs NR†‡ | <.001 | Not reported | NA |
| Kwok et al 201445 | Predominantly F-based combinations | 57 first-line (42%) | 10−4, FLC BM | 5 years; 81% vs 16%‡ | <.001 | 10 years; 53% vs 24%‡ | <.001 |
BR, bendamustine and rituximab; Clb, chlorambucil; DFS, disease-free survival; F, fludarabine; FCM, fludarabine, cyclophosphamide and mitoxantrone; F→C→R, sequential fludarabine, high-dose cyclophosphamide, and rituximab; HR, hazard ratio; NA, not applicable; NS, not significant; PB, peripheral blood.
Patients with end-of-treatment flow cytometry results only.
Significance of intermediate MRD (10−2-10−4) was dependent on the site of assessment; patients with intermediate MRD level in PB had an inferior outcome to those with this level of MRD in marrow only (although numbers were small).
MRD showed prognostic significance independent of clinical response and baseline prognostic features.