FLT3-D835 (TKD) in newly-diagnosed AML: midostaurin + 7+3 was studied in FLT3-mutant (ITD...

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ID	`BMA-FLT3-D835-AML`
Tipo	Relevância terapêutica
Estado	reviewed 2026-04-27 \| pending_clinical_signoff \| actionability review required
Doenças	`DIS-AML`
Fontes	`SRC-CIVIC` `SRC-ELN-AML-2022` `SRC-NCCN-AML-2025` `SRC-RATIFY-STONE-2017`

Fatos de ação

Biomarcador	`BIO-FLT3-D835`
Variante	Mutação de ponto TKD (D835Y/V/H/F; ~7% AML, frequentemente co-ocorrência com ITD)
Doença	`DIS-AML`
Nível ESCAT	IB
Combinações recomendadas	midostaurin + 7+3 + HiDAC consolidation + midostaurin maintenance, consider gilteritinib (off-label intensification or post-induction maintenance, trial)
Contraindicated monotherapy	quizartinib monotherapy (inactive vs D835 — type II FLT3i; QuANTUM-First label is FLT3-ITD only)
Resumo das provas	FLT3-D835 (TKD) in newly-diagnosed AML: midostaurin + 7+3 was studied in FLT3-mutant (ITD or TKD) AML in RATIFY (Stone 2017) — benefit driven primarily by ITD subset, with smaller magnitude in TKD. Quizartinib (type II FLT3i) is INACTIVE against TKD D835 (target alternate conformation). Gilteritinib (type I) and midostaurin retain activity. ELN 2022 prognostic impact of D835 alone is intermediate.

Notas

ESCAT IB. OncoKB Level 1. Critical TKI-selection point: D835 confers resistance to type II FLT3i (quizartinib, sorafenib) but NOT to type I FLT3i (gilteritinib, midostaurin, crenolanib). Companion diagnostic: LeukoStrat CDx detects both ITD and TKD D835.

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