A variante da leucemia de células peludas (HCL-V) é um linfoma raro de células B esplênicas (~10% dos casos de HCL)...
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| ID | BMA-MAP2K1-HCL |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-HCL |
| Fontes | SRC-NCCN-AML-2025 |
Fatos de ação
| Biomarcador | BIO-MAP2K1 |
|---|---|
| Variante | MAP2K1 mutação activadora (K57E, Q56P, E203K) — variante de leucemia de células peludas (HCL-V); por definição BRAF V600E-negativo |
| Doença | DIS-HCL |
| Nível ESCAT | IIA |
| Combinações recomendadas | cobimetinib 60 mg PO QD (days 1–21 of 28-day cycle) — investigational for MAP2K1-mutant HCL-V; evidence from small series only, trametinib 2 mg PO QD — alternative MEK inhibitor; same investigational status, pentostatin 4 mg/m² IV q2w + rituximab 375 mg/m² IV — standard first-line HCL-V (not biomarker-driven) |
| Resumo das provas | Hairy cell leukemia variant (HCL-V) is a rare splenic B-cell lymphoma (~10% of HCL cases) that is BRAF V600E-negative (in contrast to classic HCL where BRAF V600E is present in ~100%). MAP2K1 (MEK1) activating mutations are detected in ~40–50% of HCL-V cases and represent an alternative MAPK pathway activation mechanism. Unlike classic HCL (where vemurafenib or cladribine + rituximab are standard), HCL-V responds poorly to BRAF inhibitors and less well to purine analogues. Small series and case reports document activity of MEK inhibitors (cobimetinib, trametinib) in MAP2K1-mutant HCL-V: ORRs of 50–80% in heavily pretreated patients. No phase III RCT; no FDA approval. NCCN lists MEK inhibitors as Category 2B for HCL-V with MAP2K1 mutation. Pentostatin + rituximab remains standard first-line for HCL-V. MAP2K1 testing recommended in all HCL-V to guide salvage therapy. |
Notas
ESCAT IIA (no FDA approval; clinical evidence from small series; MAP2K1 mutation strongly predicts MEK inhibitor response in HCL-V subset). Differentiate HCL-V from classic HCL: HCL-V lacks TRAP positivity, CD25, CD123, CD11c (or dim); BRAF V600E absent; often more aggressive behavior. Standard HCL treatments (cladribine monotherapy, vemurafenib for BRAF-mutant classic HCL) are largely ineffective in HCL-V. Clinical trial enrollment preferred for MAP2K1-mutant HCL-V (basket trials of MEK inhibitors in MAPK-altered hematologic malignancies). Consider ofatumumab, bendamustine, ibrutinib (off-label) as alternatives if MAP2K1 mutation absent.
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