Table 2.
Studies using FLT3 inhibitors for relapse prevention after allo-HSCT in AML.
| Reference | FLT3 Inh | Study design | Patients number | Median age, yrs | Schedule | Response |
|---|---|---|---|---|---|---|
| Chen et al. ( 80 ) | Sorafenib | Phase 1 dose-finding |
22 | 54 (20–67) | 200–400 mg BID for 12 months | - 2-yr OS: 78% - 2-yr PFS: 72% |
| Antar et al. ( 81 ) | Sorafenib | Retrospective pilot study |
6 | 50 (32–58) | 400 mg BID | 100% are alive after median follow-up of 16 months |
| Brunner et al. ( 82 ) | Sorafenib | Retrospective 2 arms | 80 (Sorafenib: 26; Control: 54) |
- Sorafenib: 54.5 (20–74) - Control: 53 (25–72) |
200–400 mg BID for 12–24 months | - 2-yr OS: sorafenib (81%), control (62%) (S) - 2-yr PFS: sorafenib (82%), control (53%) (S) |
| Battipaglia et al. ( 83, 84 ), | Sorafenib | Retrospective Multi-center |
28 (maintenance: 25, salvage: 3) |
45 (16–57) | 200–400 mg BID | - 1-yr OS: 89 ± 7% - 1-yr LFS: 91 ± 6% - 2-yr OS: 80 ± 8% - 2-yr PFS: 73 ± 9% |
| Bazarbachi et al. ( 85 ) | Sorafenib | Retrospective EBMT registry-based analysis | 462 (Prophylaxis:19; preemptive:9; Control 434) | 50 (19–75) | 200–800 mg daily | Matched-pair analysis 26 sorafenib pts and 26 controls: - 2-yr LFS: 79% (sorafenib) and 54% (control) (S) - 2-yr OS: 83% (sorafenib) and 62% (control) (S) |
| Burchert et al. ( 86 ) SORMAIN trial | Sorafenib | Phase II prospective RCT | 83 Sorafenib: 43, Placebo: 40 |
54 (18–75) | 200–400 mg BID for up to 24 months | - 2-yr RFS: 85% (sorafenib) - 2-yr RFS: 53% (Placebo) (S) |
| Xuan et al. ( 87 ) | Sorafenib | Phase III randomized | 202 Sorafenib: 100, Placebo: 102 |
18–60 | 400 mg BID | - 2-yr LFS: 81% (sorafenib) - 2-yr LFS: 54% (Placebo) (S) - 2-yr OS: 83% (sorafenib) - 2-yr OS: 72% (Placebo) (S) |
| Maziarz et al. ( 88 ) Radius trial | Midostaurin | Phase II randomized | 60 Midostaurin + SOC: 30 Placebo + SOC: 30 |
18–70 | 50 mg BID for up to 12 months | - 1.5-yr RFS: 89% (midostaurin + SOC) - 1.5-yr RFS: 76% (Placebo + SOC) |
| Schlenk et al. ( 89 ) | Midostaurin | Phase II prospective |
134 (Midostaurin: 75, Control:59) |
18–70 | 50 mg BID for 12 months | Landmark analysis: Better EFS and OS in midostaurin pts (S) |
| Sandmaier et al. ( 90 ) | Quizartinib | Phase 1 Dose finding |
13 | 43 (23–61) | 40 mg daily (n = 7) 60 mg daily (n = 6) |
- One relapse among 13 patients |
Inh, inhibitor; yrs, years; OS, overall survival; PFS, progression-free survival; DFS, disease-free survival; S, significant; LFS, leukemia-free survival; RFS, relapse-free survival; SOC, standard of care.