Table 3.

Clinical trials of FLT3 inhibitors as maintenance therapy after stem cell transplantation in AML patients.

Agent (Reference Number)	Study Design and Population	Therapeutic Schedule	Treatment Outcomes	Adverse Effects
First generation FLT3 inhibitors
Midostaurin [69]	Phase II (n = 60), 18–70 yrs FLT3 mutation, required	Midostaurin -50 mg bid/d for 12 d in 4-wk cycle	18-mo RFS—89% in midostaurin arm vs, 76% in Standard-Of-Care arm (p = 0.27). some pts with higher levels of FLT3 inhibition -prolonged RFS (p = 0.06) and improved survival (p= 0.048) → midostaurin, clinical benefit in some FLT-ITD+ pts.	Vomiting, Nausea, Fatigue, Diarrhea
Sorafenib [70]	Phase II (n = 83) FLT3-ITD+ pts in CR after SCT	Sorafenib, 200–800 mg/d, +60–+100 d  after SCT. during 24 months, Tx—continuously at 24 mo	Relapse/death risk, lower in sorafenib arm vs. placebo arm (HR = 0.39, p = 0.013) 24 mo-RFS 53.3% vs. 85.0% (HR = 0.256; p = 0.002) → Sorafenib maintenance, reduce risk of relapse and death  after SCT for FLT-ITD+ AML.
Sorafenib [71]	Phase III (n = 202), 18–60 yrs	400 mg bid/d at 30–60 post-SCT.	1-yr cumulative relapse in sorafenib arm, 7.0%  vs. 24.5% in control arm (p = 0.0010) → sorafenib maintenance, reduce relapse and well-tolerable	Infection, Acute/chronic GVHD, Hematologic toxicity
Midostaurin (NCT01477606)	Phase II (n = 284), 18–70 yrs 18–60 yrs (n = 198) 61–70 yrs (n = 86)		CR/Cri—76.4% (younger, 75.8%/older, 77.9%) 2-yr CIR in SCT (18.1% and 17.6% in younger and older) -lower than CTx alone (39.2% and 56.4%) 2-yr CIR in maintenance group, 13.3% -lower than HDAC CTx alone 43.5% (p = 0.02)	QTc prolongation Lung toxicity, Diarrhea, Mucositis, Cytoepnia

RFS, relapse-free survival; HR, hazard ratio; SCT; relapse-free survival; SCT, stem cell transplantation; HR, hazard ratio; CRi, complete remission with incomplete count recovery; GVHD, graft-versus-host disease; CIR, the cumulative incidence of remission; HDAC, high dose ara-C.