FLT3-D835 (TKD) in newly-diagnosed AML: midostaurin + 7+3 was studied in FLT3-mutant (ITD...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-FLT3-D835-AML |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-AML |
| Sources | SRC-CIVIC SRC-ELN-AML-2022 SRC-NCCN-AML-2025 SRC-RATIFY-STONE-2017 |
Actionability Facts
| Biomarker | BIO-FLT3-D835 |
|---|---|
| Variant | TKD point mutation (D835Y/V/H/F; ~7% AML, often co-occurs with ITD) |
| Disease | DIS-AML |
| ESCAT tier | IB |
| Recommended combinations | 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) |
| Evidence summary | 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. |
Notes
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.
Used By
No reverse references found in the YAML corpus.