Summary of important studies with patients with MDS and reported MRD results including allogeneic HCT
| Study . | Population . | Study design . | Intervention . | MRD methodology . | Results . |
|---|---|---|---|---|---|
| Mixed populations, including palliative therapy | |||||
| Welch et al98 | MDS (n = 26), AML (de novo, n = 54; relapsed, n = 36) | Prospective, uncontrolled trial (n = 84) and extension cohort (n = 32) | 10-day or 5-day decitabine | WES and NGS gene panel (LOD not specified) | Rate of any mutation clearance associated with morphological response |
| Hunter et al95 | MDS (n = 210), MDS/MPN (n = 16), AML (N = 102), and t-MN (n = 60) | Retrospective | HMA therapy (7% additional agents) | NGS gene panel (VAF ≥5%) | TP53 mutation clearance associated with longer median survival (15.6 [negative] vs 7.7 [positive] months; P = .001) |
| Sallman et al97 | MDS (n = 40), AML (n = 11), and MDS/MPN (n = 4) | Phase 1b/2 | Eprenetapopt plus azacitidine | NGS (PB; LOD 0.1%) | TP53 mutation clearance associated with CR |
| Steensma et al83 | ESA relapsed/ refractory lower-risk MDS (N = 57) | Phase 2 | Imetelstat | NGS (BM and PB) | SF3B1 VAF reduction correlated with duration of transfusion independence |
| Yun et al84 | MDS (n = 95), secondary AML (n = 52), and MDS/MPN (n = 10) | Retrospective | HMA (74%), intensive chemotherapy (45%), and HCT (24%) | NGS gene panel (BM and PB; MRD VAF ≥5%) | MRD negativity (median OS not reached vs 18.5 months; P = .002) and TP53 mutation clearance <5% were associated with better OS |
| Sallman et al100 | MDS (N = 95) | Phase 1b | Magrolimab plus azacitidine | MFC (LOD 0.02%) | Small, heterogeneous high-risk cohort with 26% TP53 mutant MDS CR rate 33%, MRD negativity rate 23% Trend for improved OS in patients who became MRD– |
| Nannya et al 85 | MDS (n = 384) | Retrospective | Azacitidine | NGS gene panel (≥1%; LOD not specified) | Except for DDX41, posttreatment (≥ 4 cycles) clone size correlated with response observations |
| Before transplant | |||||
| Festuccia et al27 | MDS (n = 285; 23% had advanced to AML before HCT) CMML (n = 4) | Retrospective | HCT | MFC-MRD (LOD 0.001%-0.1%) plus cytogenetics/FISH | MRD status associated with CIR |
| Dillon et al71 | MDS (N = 48) | Subgroup analysis of a prospective phase 3 trial | RIC (n = 23) vs MAC (n = 25) | NGS 10-gene panel (PB) | MRD status associated with OS (55% vs 79%; P = .045) and CIR (40% vs 11%; P = .022) at 3 years Higher relapse rate in MRD+ patients randomly assigned to RIC vs MAC: 60% vs 8% (P = .010) |
| Craddock et al 23,112 | AML (n = 164) and MDS (n= 80) | Phase 2 randomized trial | Standard RIC (n = 108) vs intensified FLAMSA-Bu RIC (n = 108)` | MFC (BM; LOD 0.02%-0.05%) | Pretransplant MRD positivity associated with 2-year CIR in MDS: 50.0% vs 21.1% (P = .020) |
| Ma et al 119 | MDS-EB (n = 103) | Retrospective | HCT | MFC (BM; LOD <0.01%-0.05%) | MRD status associated with DFS and OS |
| After transplant | |||||
| Bernal et al26 | AML (n = 49) and MDS (n = 38) | Retrospective | MAC (16%) and RIC (84%) | MFC (BM; >0.01%) | Positive pretransplant MRD associated with positive MRD on day +100 Positive MRD on day +100 associated with relapse (OR, 6.55) |
| Duncavage et al114 | MDS (N = 90) | Retrospective | RIC (42%) and MAC (58%) | NGS (BM; VAF ≥0.5%) | 37% of patients tested as MRD+ on day +30 and 31% on day +100 MRD positivity on days +30 and +100 was associated with higher risk of disease progression or death |
| Nakamura et al 49 | AML (n= 37) and MDS (n = 14) | Retrospective | HCT (MAC 100%; 92% cord blood) | Personalized droplet digital PCR assay (circulating tumor DNA from serum or DNA from matched BM; median LOD 0.04%) | MRD positivity (either BM or serum) at 1 and 3 months associated with higher 3-year CIR and risk of death Greater or equal to 1.5-fold increase in ctDNA between 1 and 3 months after HCT was associated with highest risk of relapse (HR = 28.5; P = .0001) and death (HR, 17.4; P = .0009) |
| Study . | Population . | Study design . | Intervention . | MRD methodology . | Results . |
|---|---|---|---|---|---|
| Mixed populations, including palliative therapy | |||||
| Welch et al98 | MDS (n = 26), AML (de novo, n = 54; relapsed, n = 36) | Prospective, uncontrolled trial (n = 84) and extension cohort (n = 32) | 10-day or 5-day decitabine | WES and NGS gene panel (LOD not specified) | Rate of any mutation clearance associated with morphological response |
| Hunter et al95 | MDS (n = 210), MDS/MPN (n = 16), AML (N = 102), and t-MN (n = 60) | Retrospective | HMA therapy (7% additional agents) | NGS gene panel (VAF ≥5%) | TP53 mutation clearance associated with longer median survival (15.6 [negative] vs 7.7 [positive] months; P = .001) |
| Sallman et al97 | MDS (n = 40), AML (n = 11), and MDS/MPN (n = 4) | Phase 1b/2 | Eprenetapopt plus azacitidine | NGS (PB; LOD 0.1%) | TP53 mutation clearance associated with CR |
| Steensma et al83 | ESA relapsed/ refractory lower-risk MDS (N = 57) | Phase 2 | Imetelstat | NGS (BM and PB) | SF3B1 VAF reduction correlated with duration of transfusion independence |
| Yun et al84 | MDS (n = 95), secondary AML (n = 52), and MDS/MPN (n = 10) | Retrospective | HMA (74%), intensive chemotherapy (45%), and HCT (24%) | NGS gene panel (BM and PB; MRD VAF ≥5%) | MRD negativity (median OS not reached vs 18.5 months; P = .002) and TP53 mutation clearance <5% were associated with better OS |
| Sallman et al100 | MDS (N = 95) | Phase 1b | Magrolimab plus azacitidine | MFC (LOD 0.02%) | Small, heterogeneous high-risk cohort with 26% TP53 mutant MDS CR rate 33%, MRD negativity rate 23% Trend for improved OS in patients who became MRD– |
| Nannya et al 85 | MDS (n = 384) | Retrospective | Azacitidine | NGS gene panel (≥1%; LOD not specified) | Except for DDX41, posttreatment (≥ 4 cycles) clone size correlated with response observations |
| Before transplant | |||||
| Festuccia et al27 | MDS (n = 285; 23% had advanced to AML before HCT) CMML (n = 4) | Retrospective | HCT | MFC-MRD (LOD 0.001%-0.1%) plus cytogenetics/FISH | MRD status associated with CIR |
| Dillon et al71 | MDS (N = 48) | Subgroup analysis of a prospective phase 3 trial | RIC (n = 23) vs MAC (n = 25) | NGS 10-gene panel (PB) | MRD status associated with OS (55% vs 79%; P = .045) and CIR (40% vs 11%; P = .022) at 3 years Higher relapse rate in MRD+ patients randomly assigned to RIC vs MAC: 60% vs 8% (P = .010) |
| Craddock et al 23,112 | AML (n = 164) and MDS (n= 80) | Phase 2 randomized trial | Standard RIC (n = 108) vs intensified FLAMSA-Bu RIC (n = 108)` | MFC (BM; LOD 0.02%-0.05%) | Pretransplant MRD positivity associated with 2-year CIR in MDS: 50.0% vs 21.1% (P = .020) |
| Ma et al 119 | MDS-EB (n = 103) | Retrospective | HCT | MFC (BM; LOD <0.01%-0.05%) | MRD status associated with DFS and OS |
| After transplant | |||||
| Bernal et al26 | AML (n = 49) and MDS (n = 38) | Retrospective | MAC (16%) and RIC (84%) | MFC (BM; >0.01%) | Positive pretransplant MRD associated with positive MRD on day +100 Positive MRD on day +100 associated with relapse (OR, 6.55) |
| Duncavage et al114 | MDS (N = 90) | Retrospective | RIC (42%) and MAC (58%) | NGS (BM; VAF ≥0.5%) | 37% of patients tested as MRD+ on day +30 and 31% on day +100 MRD positivity on days +30 and +100 was associated with higher risk of disease progression or death |
| Nakamura et al 49 | AML (n= 37) and MDS (n = 14) | Retrospective | HCT (MAC 100%; 92% cord blood) | Personalized droplet digital PCR assay (circulating tumor DNA from serum or DNA from matched BM; median LOD 0.04%) | MRD positivity (either BM or serum) at 1 and 3 months associated with higher 3-year CIR and risk of death Greater or equal to 1.5-fold increase in ctDNA between 1 and 3 months after HCT was associated with highest risk of relapse (HR = 28.5; P = .0001) and death (HR, 17.4; P = .0009) |
A more extensive version of this table can be found in supplemental Table 2.
CIR, cumulative incidence of relapse; CMML, chronic myelomonocytic leukemia; DFS, disease-free survival; DTA, DNMT3A, TET2, and ASXL1; ESA, erythropoiesis-stimulating agent; FISH, fluorescence in situ hybridization; FLAMSA-Bu, fludarabine, cytarabine, amsacrine, and busulfan; HR, hazard ratio; MAC, myeloablative conditioning; MDS-EB, MDS with excess blasts; MPN, myeloproliferative neoplasm; OR, odds ratio; PCR, polymerase chain reaction; RIC, reduced intensity conditioning; t-MN, therapy-related myeloid neoplasm; WES, whole-exome sequencing.