Les mutations activantes JAK3 sont détectées dans environ 35 % des sous-types ATLL agressifs (aigus et lym...
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| ID | BMA-JAK3-ATLL |
|---|---|
| Type | Pertinence thérapeutique |
| État | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Maladies | DIS-ATLL |
| Sources | SRC-ESMO-PTCL-2024 |
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| Biomarqueur | BIO-JAK3 |
|---|---|
| Variante | mutation activatrice JAK3 (A572V, A573V, M511I le plus fréquent) — leucémie/lymphome des cellules T adultes (ATLL); sous-types principalement agressifs (aigus et lymphomes) |
| Maladie | DIS-ATLL |
| Niveau ESCAT | IIA |
| Combinaisons recommandées | ruxolitinib 20 mg PO BID (investigational in ATLL; dose per MF/GVHD approval; JAK3-mutant subset; clinical trial preferred), mogamulizumab 1 mg/kg IV (approved for CTCL in US; used off-label for ATLL; CCR4-targeted, not JAK3-specific), VCAP-AMP-VECP chemotherapy (standard aggressive ATLL per Japanese guidelines) |
| Résumé des faits | JAK3 activating mutations are detected in ~35% of aggressive ATLL subtypes (acute and lymphoma types) and activate downstream STAT3/STAT5 independent of cytokine stimulation. Ruxolitinib (JAK1/2 inhibitor; FDA-approved for myelofibrosis, PV, GVHD, CTCL) has documented activity in JAK3-mutant ATLL: case series and retrospective analyses report ORRs of 40–67% in relapsed/refractory ATLL; single-arm phase II data is limited. No FDA approval for ATLL specifically. Mogamulizumab (anti-CCR4, FDA 2018 for CTCL) is approved for relapsed/refractory CTCL and ATLL in Japan; FDA approval is CTCL only in US — CCR4 expression is present in ~90% of ATLL independent of JAK3 status. JAK3 mutation confers worse prognosis in ATLL and identifies a subset potentially responsive to JAK pathway inhibition. ESCAT IIA: biomarker predicts response to an investigational (in ATLL context) therapy class (JAK inhibitors). |
Notes
ESCAT IIA: JAK3 mutation predicts JAK inhibitor sensitivity in ATLL; no regulatory approval in ATLL for JAK inhibitors as of 2026. ATLL is caused by HTLV-1 (Human T-cell Leukemia Virus 1) and is endemic in Japan, the Caribbean, and parts of Africa/South America. Molecular landscape: JAK3 mutations (~35%), CCR4 mutations (~25%), RHOA G17V (~20%), PD-L1 amplification. Mogamulizumab (CCR4-targeted) has activity in ATLL independent of JAK3 status and is standard in Japan. Allogeneic HCT is potentially curative for fit patients with aggressive ATLL in CR. Ruxolitinib access: JAK3 mutation testing should be performed in all relapsed ATLL; if positive, ruxolitinib off-label or via compassionate use/basket trial is a reasonable option when standard therapies fail.
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