OnCo
pairingsPairing

FLT3 inhibitor + intensive chemotherapy

Adding a FLT3 blocker to standard chemotherapy is the proven way to improve survival in FLT3-mutated AML.

RATIFY (midostaurin, HR 0.78) and QuANTUM-First (quizartinib, HR 0.776) both improved OS; maintenance after transplant adds further protection (MORPHO, gilteritinib, in MRD-positive patients).

Quizartinib+Cytarabine + anthracycline ('7+3')combination
Rationale
Chemotherapy debulks; FLT3 inhibition removes the proliferative driver and suppresses the resistant subclone that would otherwise relapse.
Evidence
Two positive phase 3 trials with different molecules.

Key papers

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rctThe Lancet 2023changed practice
QuANTUM-First: quizartinib added to intensive chemotherapy and continued as maintenance in newly diagnosed FLT3-ITD AML

QuANTUM-First gave FLT3-ITD AML patients a second front-line targeted option and showed that continuing a FLT3 inhibitor as long-term maintenance, including after transplant, pays off. Quizartinib was approved for this indication in 2023. Head-to-head data against midostaurin are lacking, and the design leaves open how much of the benefit came from maintenance.

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cancers

1
Acute myeloid leukaemia

targets

1
FLT3

drugs

4
Not mapped hereCytotoxic regimen
Cytarabine + anthracycline ('7+3')
ApprovedSmall-molecule kinase inhibitor (FLT3, type I)
Gilteritinib · Xospata
ApprovedSmall-molecule multikinase inhibitor (FLT3)
Midostaurin · Rydapt
ApprovedSmall-molecule kinase inhibitor (FLT3-ITD, type II)
Quizartinib · Vanflyta

trials

2
QuANTUM-FirstRATIFY (CALGB 10603)

key papers

1
QuANTUM-First: quizartinib added to intensive chemotherapy and continued as maintenance in newly diagnosed FLT3-ITD AML