Background
Hypomethylating agents
References | Study design | Patients, N | Maintenance therapy regimen | Relapse | Survival |
---|---|---|---|---|---|
Jabbour [14] | Retrospective, single arm | 8 acute leukemia (7 AML, 1 ALL) | low-dose AZA daily × 5 days every 28 days for a median of 8 cycles | 3/8 (37.5%) | 5 alive with CR, 2 alive with leukemia |
de Lima [15] | Phase I | 45 high-risk AML/ MDS (37 AML, 8 MDS) | low-dose AZA daily × 5 days every 30 days for a maximum of 4 cycles | 24/45 (53.3%) | 1-year OS: 77%; 1-year LFS: 58% |
Maples [18] | Retrospective, 2 arms | 25 (18 AML, 7 MDS) | AZA 32 mg/m2/day × 5 days every 28 days for 4–6 cycles | 16% (AZA) versus 14% (Control) | 1-year OS: 60% (AZA) versus 64% (Control) |
Oshikawa [19] | Retrospective, 2 arms | 10 high-risk AML | AZA (30 mg/m2/day on days 1–7) and GO (3 mg/m2 on day 8) every 4 weeks for up to 4 cycles | AZA-GO: 4/10 (40.0%) | AZA-GO versus Control 1-year OS: 70.0% versus 59.8%; 1-year LFS: 60.0% versus 42.8% |
Pusic [16] | Phase I | 22 (17 AML, 5 MDS) | DAC × 5 days every 6 weeks for a maximum of 8 cycles | 2-year CIR: 28% | 2-year OS: 56%; 2-year LFS: 48% |
Ma [17] | Retrospective, 2 arms | 21 high-risk AML | DAC 20 mg/m2/day × 5 days every 3 months for up to 4–6 cycles | 3-year CIR: 5.9% (DAC) versus 45.3% (Control) | 3-year OS: 92.9% (DAC) versus 51.8% (Control) |
Platzbecker [20] | Phase II | 24 high-risk AML or MDS with MRD-positive post-transplantation | preemptive therapy with AZA 75 mg/m2/day on days 1–7 of a 29-day cycle for a minimum of 6 cycles | 8/24 (33.3%) | 2-year OS: 62%; 2-year LFS: 54%, |
de Lima [21] | Phase I/II | 30 (26 AML, 4 MDS) | CC-486 daily × 7 days every 28 days for up to 12 cycles | 1-year CIR: 21% | 1-year OS in the 7-day and 14-day dosing cohorts of 86% and 81% |
Gao [22] | Phase II RCT | 202 high-risk MRD- negative AML (G-DAC: 100; Non-G-DAC: 102) | G-DAC: 5 mg/m2 of DAC on days 1–5 and 100 mg/m2 of rhG-CSF on days 0–5 every 6–8 weeks for up to 6 cycles; Non-G-DAC: no intervention | 2-year CIR: 15.0% (G-DAC) versus 38.3% (Non-G-DAC) | G-DAC versus Non-G-DAC 2-year OS: 85.8% versus 69.7%; 2-year LFS: 81.9% versus 60.7% |
FLT3 inhibitors
References | Study design | Patients, N | Flt3 inhibitors, maintenance duration | Relapse | Survival |
---|---|---|---|---|---|
Chen [29] | Phase I | 22 FLT3-ITD AML | Sorafenib, 12 months | 3/22 (13.6%) | 1-year OS: 95%; 1-year LFS: 85% |
Brunner [30] | Retrospective, 2 arms | 81 FLT3-ITD AML (Sorafenib: 26; Control: 55) | Sorafenib, median duration of 336.5 (19–1556) days | 2-year CIR: 8.2% (Sorafenib) versus 37.7% (Control) | Sorafenib versus Control 2-year OS: 81% versus 62%; 2-year LFS: 82% versus 53% |
Battipaglia [31] | Retrospective, single arm | 27 FLT3-mutated AML (25 FLT3- ITD, 2 FLT3-TKD) | Sorafenib, median duration of 8.4 (0.2–46) months | 3/27 (11.1%) | 2-year OS: 80% ± 8% 2-year LFS: 73% ± 9% |
Xuan [25] | Retrospective, 2 arms | 144 FLT3-ITD AML (Sorafenib: 58; Control: 86) | Sorafenib, median duration of 146 (51–240) days | 3-year CIR: 17.3% (Sorafenib) versus 34.2% (Control) | Sorafenib versus Control 3-year OS: 81.3% versus 62.9%; 3-year LFS: 79.3% versus 52.1% |
Bazarbachi [33] | Retrospective, EBMT registry-based analysis | 462 FLT3-mutated AML (Sorafenib: 28; Control: 434) | Sorafenib, median duration of ≥ 12 months | 2-year CIR of total 462 patients: 34% | Matched-pair analysis 26 sorafenib patients versus 26 controls: 2-year OS: 83% versus 62%; 2-year LFS: 79% versus 54% |
Xuan [35] | Phase III RCT | 202 FLT3-ITD AML (Sorafenib: 100; Control: 102) | Sorafenib was administered at 30–60-day post-transplantation and continued until day 180 | Sorafenib versus Control 1-year CIR: 7.0% versus 24.5%; 2-year CIR: 11.9% versus 31.6% | Sorafenib versus Control 2-year OS: 82.1% versus 68.0%; 2-year LFS: 78.9% versus 56.6% |
Burchert [36] | Phase II RCT (SORMAIN, terminated early due to slow accrual) | 83 FLT3-ITD AML (Sorafenib: 43; Placebo: 40) | Sorafenib, 24 months | Sorafenib (8/43, 18.6%) versus Placebo (17/40, 42.5%) | Sorafenib versus Placebo 2-year OS: 90.5% versus 66.2%; 2-year LFS: 85.0% versus53.3% |
Sandmaier [40] | Phase I | 13 AML | Quizartinib (AC220), a maximum of 24 months | 1/13 (7.7%) | NA |
Maziarz [42] | Phase II RCT (the preliminary result) | 60 FLT3-ITD AML (Midostaurin + SOC: 30; SOC: 30) | Midostaurin, 12 months | 18-month estimated relapse rate: 11% (Midostaurin + SOC) versus 24% (SOC) | 18-month LFS: 89% (Midostaurin + SOC) versus 76% (SOC) |
Levis [43] | Phase III RCT (Ongoing, NCT02997202) | 346 FLT3-ITD AML (target number, Gilteritinib: 173; Placebo: 173) | Gilteritinib, 2 years | NA | NA |