Table 1 Summary of FLT3 inhibitors and mechanisms of resistance observed

Midostaurin

First

I

FLT3, PKC, KIT, PDGFR, VEGF, CDK1, etc

Approved for newly diagnosed FLT3 mutant AML patients in combination with chemotherapy

Upregulation of MCL-1 [61, 62], FLT3-N676K mutation [63]

Sorafenib

First

II

FLT3, VEGFR, KIT, RET, PDGFR

RAF-1, ERK

Phase III (NCT02156297), used off-label

FLT3-D835Y, F691L, Y842D mutations [44, 48, 64, 65], increased PIM expression [66], ERK activation [67]

Sunitinib

First

I

PDGFR, KIT, VEGFR, RET

Phase I and II (NCT00783653)

Loss of FLT3 [68]

Ponatinib

First

II

FLT3, BCR-ABL, VEGFR

Phase I/II (NCT02428543), (NCT02829840)

FLT3-D835Y mutation [69]

Quizartinib

Second

II

FLT3, KIT, PDGFR

Phase III (NCT02668653)

FLT3-D835Y, F691L, Y842D mutations [48, 70], ERK activation [67]

Gilteritinib

Second

I

FLT3, AXL

Approved for FLT3 mutant adult AML patients who failed or are refractory to previous treatment

FLT3-F691L mutation, N-Ras signaling [71]

Crenolanib

Second

I

FLT3, PDGFR

Phase III (NCT03258931)

N-Ras, IDH2, TET2 [72], FLT3-K429E, F691L [69, 73]