Table 3.
HMAs in the maintenance therapy: clinical results from prospective trials. Abbreviations: CR: complete remission, PR: partial remission, CRi: complete remission with incomplete hematologic recovery, MLFR: myeloid leukemia free state, no resp: no response, SD: stable disease, CIR: cumulative incidence of relapse, ORR: overall response rate, OS: overall survival, RFS: relapse-free survival, EFS: event-free survival, AML: acute myeloid leukemia, MDS: myelodysplastic syndrome, AZA: azacitidine, DAC: decitabine, mo: months, na: not applicable, DLI: donor lymphocyte infusion, rh-G-CSF: recombinant-human granulocyte colonies-stimulating factor.
| Authors | Number of Patients | Study Design | Schedule of Administration | Relapse | Outcome |
|---|---|---|---|---|---|
| De Lima et al., 2010 [113] | 45 (37 AML, 8 MDS) | Open Label, dose escalation, Phase I | Optimal: AZA 32 mg/m2 dd 1–5 25-day cycle |
20 mts follow-up CIR: 53% | 1-year EFS: 55% 1-year OS: 77% |
| Pusic I et al., 2015 [114] | 22 evaluable (17 AML, 5 MDS) | Open Label, dose escalation, Phase I | Optimal: DAC 10 mg/m2 dd 1–5 6-wks cycle |
2-year CIR: 28% | 2-year DFS: 48% 2-year OS: 56% |
| Craddock C. et al., 2016 [78] | 37 AML | Open Label, Single-Arm, Phase II | AZA 36 mg/m2 days 1–5 | Median time to relapse: 8 months | 2-year RFS: 49% 2-year OS: 49% |
| De Lima et al., 2018 [116] | 30 (26 AML, 4 MDS) | Open Label, 3+3 dose escalation, Phase I/II | Oral AZA. 4 dose-levels: 200 mg for 7 days 300 mg for 7 days 150 mg for 14 days 200 mg for 14 days |
1-year CIR: 43% 7-days group; 13% 14-days group | Median OS: not reached. Estimated 1-year OS: 81% for 7-day group, 86% for 14-day group |
| Guillaume T. et al., 2019 [117] | 30 (20 AML, 10 MDS) | Open Label, Single-Arm (compared with historical cohort not receiving AZA or DLIs), Phase II | AZA 32 mg/m2 days 1–5 + DLI | 2-year CIR: 27%. (41% in historical cohort, p = 0.2) | 2-year DFS: 65.5% 2-year OS: 65.5% |
| Oran B. et al., 2020 [118] | 187 (140 AML, 47 MDS) | Randomized 1:1, Open Label, Double Arm, Phase III | AZA 32 mg/m2 days 1–5 vs. observation only | 1-year CIR: 41% vs. 39%p = ns | RFS: 2.07 y vs. 1.28 y (p = ns) OS: 2.52 y vs. 2.56 y (p = ns) |
| Lei Gao et al., 2020 [120] | 204 AML | Randomized 1:1, Open Label, Double Arm, Phase III | rhG-CSF 100 µg/m2 days 0–5 + DAC 5 mg/m2 days 1–5 vs. observation only | 2-year CIR: 38% vs. 15% (p < 0.01) |
2-year LFS: 81.9% vs. 60.7% 2-year OS: 85.8% vs. 69.7% |