Table 1.
HMAs in the treatment of overt relapse: clinical results from retrospective and 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, HMAs: hypomethylating agents, CHT: chemotherapy.
| Authors | Number of Patients | Study Design | Schedule of Administration | Response | p-Value | Outcome | p-Value |
|---|---|---|---|---|---|---|---|
| Craddock et al., 2016 [78] | 181 (116 AML, 65 MDS) | Retrospective | AZA 75 mg/m2 for 5–7 days | CR: 8% > 2 risk factors; CR: 34% no risk factors |
p < 0.0019 | 2-year OS: 3% > 2 risk factors; 37% no risk factors |
p < 0.00001 |
| Motabi I et al., 2016 [79] | 100 (CHT: 73 vs HMAs: 27) |
Retrospective | AZA 75 mg/m2 for 5 days + DLI (55% and 33% of pts, respectively) | CR/CRi 51% vs. 19% |
p < 0.004 | Median PFS:4.9 vs. 3.8 months In favour of CHT |
p < 0.02 |
| Schroeder et al., 2018 [80] | 36 (29 AML, 7 MDS) | Retrospective | DAC 20 mg/m2 for 5 days (67%) or 10 days (33%) | ORR: 25% CR: 17% PR: 8% |
na | 2-year OS: 11% (±6%) | na |
| Schroeder et al., 2013 [84] | 30 (28 AMl, 2 MDS) | Prospective, Open Label, Single-Arm, Phase II | AZA 100 mg/m2 for 5 days + DLI | ORR: 30% CR: 23% PR: 7% |
na | Median OS 117 mo (not reached for pts in CR, 83 days for pts without CR) |
p < 0.001 in favour of patients achieving CR |
| Ghobadi A. et al., 2016 [79] | 8 AML | Prospective, Open Label, 3 + 3 dose escalation, Phase I | AZA 45 mg/m2 (37%) and 75 mg/m2 (63%) at days 4-6-8-10 after DLI | ORR: 75% CR/CRi: 50% Cytogenetic remission: 25% |
na | Median DFS: 2.9 mo Median OS: 12.5 mo |
na |
| Craddock C. et al., 2019 [86] | 29 (24 AML, 5 MDS) | Prospective, Open Label, Dose finding, Phase I | AZA 75 mg/m2 for 7 days + Lenalidomide (4 dose-levels: 5-10-15-25 mg) |
ORR: 47% CR/CRi: 40% PR: 6% |
na | Median OS: 10 mo for not-responders, 27 mo for responders |
p = 0.004 in favour of responders |
| Woo J. et al., 2017 [87] | 39 (26 AML, 13 MDS) | Prospective Open-label, Single-Arm, Phase II | AZA 75 mg/m2 for 7 days | ORR: 30.7% CR: 8% PR: 23% |
na | 2-year OS: 25% 71 % in responders) |
na |
| Zhao P. et al., 2021 [90] | 26 AML | Prospective Open-label, Single-Arm, Phase II | AZA 75 mg/m2 for 5 days + Venetoclax followed by DLI | ORR: 61.5% CR: 26.9% PR: 34.6% |
na | Median EFS: 120 days Median OS: 284.5 days |
na |