Table 2 Key studies of FLT3 inhibitors as maintenance therapy in AML patients after allo-HSCT
References | Study design | Patients, N | Flt3 inhibitors, maintenance duration | Relapse | Survival |
|---|---|---|---|---|---|
Chen [29] | Phase I | 22 FLT3-ITD AML | Sorafenib, 12Â 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, 24Â 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 24Â 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, 2Â years | NA | NA |