Creme de Ruxolitinib (Opzelura) recebeu aprovação da FDA (Setembro 2022) para...
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| ID | BMA-JAK3-CTCL |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-MF-SEZARY |
| Fontes | SRC-ESMO-CTCL-2024 |
Fatos de ação
| Biomarcador | BIO-JAK3 |
|---|---|
| Variante | Ativação da mutação JAK3 — micose fungoides (MF) ou síndrome de Sézary (SS); hiperativação da via JAQ/STAT; ruxolitinib aprovado para MF/SS independentemente do estado JAH3 |
| Doença | DIS-MF-SEZARY |
| Nível ESCAT | IIA |
| Combinações recomendadas | ruxolitinib 20 mg PO BID — investigational for JAK3/JAK1-altered MF/SS; no approved CTCL indication for oral ruxolitinib, mogamulizumab 1 mg/kg IV weekly ×4 then q2w — FDA-approved for relapsed/refractory MF/SS (CCR4-targeted; JAK3-independent), brentuximab vedotin 1.8 mg/kg IV q3w — FDA-approved for CD30+ MF (CD30 ≥10% by IHC; JAK3-independent) |
| Resumo das provas | Ruxolitinib cream (Opzelura) received FDA approval (September 2022) for mild-to-moderate atopic dermatitis; separately, ruxolitinib phosphate (Jakafi, oral) is FDA-approved for steroid-refractory acute/chronic GVHD but NOT specifically approved for CTCL as of 2026. However, the JAK/STAT pathway is aberrantly activated in MF/SS (~30–50% have JAK3 mutations or JAK1/STAT3/STAT5 alterations), making JAK inhibitors an active investigational area. Phase II evidence: ruxolitinib (oral) ORR ~29% in relapsed/refractory MF (RUXO-MF pilot data); itacitinib (JAK1 inhibitor) and cerdulatinib (JAK/SYK inhibitor) in phase II trials for CTCL. The CTCL-specific approvals are for non-JAK-targeted agents: romidepsin (HDAC inhibitor; FDA 2009 CTCL), brentuximab vedotin (CD30+; FDA 2017), mogamulizumab (CCR4; FDA 2018), vorinostat (FDA 2006). JAK3-mutant CTCL: JAK3 mutation identifies a subset with stronger a priori rationale for JAK inhibitor use; ESCAT IIA reflects absence of dedicated FDA approval in CTCL despite biological rationale and early phase data. |
Notas
ESCAT IIA: JAK3 mutation enriches for JAK inhibitor sensitivity in CTCL; no FDA-approved JAK inhibitor for oral CTCL use as of 2026. Clinical decision: JAK3 testing in MF/SS informs trial eligibility for JAK inhibitor basket trials; does not currently change standard therapy sequence. Standard sequence for MF/SS: skin-directed therapy (topical steroids, phototherapy PUVA/UVB) → bexarotene → mogamulizumab or brentuximab vedotin (CD30+) → romidepsin → clinical trial (including JAK inhibitor trials for JAK-altered disease). Itacitinib (JAK1-selective) and cerdulatinib (JAK/SYK) have phase II CTCL data; watch for label updates. Note: mogamulizumab is CCR4-targeted (not JAK3-specific) and is FDA-approved for R/R MF/SS regardless of JAK3 status.
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