Patient
BMA-JAK3_CTCL · Algorithm: ALGO-MF-SEZARY-1L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| BIO-JAK3 | JAK3 activating mutation — mycosis fungoides (MF) or Sézary syndrome (SS); JAK/STAT pathway hyperactivation; ruxolitinib approved for MF/SS regardless of JAK3 status | IIA | - SRC-ESMO-CTCL-2024: Level B (Supports, Sensitivity/Response)
| 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. | 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) | |
Treatment options (3 tracks)
- Indication
- IND-MF-EARLY-1L-SKIN-DIRECTED
- Regimen
- —
- Reason
- Engine default per algorithm ALGO-MF-SEZARY-1L: {'step': 1, 'outcome': False, 'branch': {'result': 'IND-MF-EARLY-1L-SKIN-DIRECTED'}, 'fired_red_flags': [], 'winner_red_flag': None}
- Indication
- IND-MF-ADVANCED-1L-MOGA
- Regimen
- Mogamulizumab monotherapy (1.0 mg/kg IV weekly × 5, then q2 weeks)
- Drugs + NSZU
- Mogamulizumab (DRUG-MOGAMULIZUMAB) 1.0 mg/kg · IV over ≥1h weekly × 5 (induction); then every 2 weeks until progression or toxicity · IV ✗ Not registered in UA
- Reason
- Alternative track presented for HCP consideration
- Indication
- IND-MF-ADVANCED-1L-BV
- Regimen
- Brentuximab vedotin monotherapy for CD30+ MF/cutaneous ALCL (1.8 mg/kg IV q3 weeks)
- Drugs + NSZU
- Brentuximab vedotin (DRUG-BRENTUXIMAB-VEDOTIN) 1.8 mg/kg (max 180 mg) · IV over 30 min every 21 days × up to 16 cycles or progression / toxicity · IV ✓ NSZU covered
- Hard contraindications
- CI-BORTEZOMIB-SEVERE-NEUROPATHY
- Reason
- Alternative track presented for HCP consideration
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CD20-IHC | CD20 Immunohistochemistry | Critical | histology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-FLOW-CYTOMETRY | Flow Cytometry | Critical | histology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-HBV-SEROLOGY | Hepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs) | Critical | lab | — | all tracks |
| TEST-HCV-ANTIBODY | HCV Antibody | Critical | lab | — | all tracks |
| TEST-HIV-SEROLOGY | HIV Antibody/Antigen | Critical | lab | — | all tracks |
| TEST-LDH | Lactate Dehydrogenase | Critical | lab | — | all tracks |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-ECHO | Echocardiography | Standard | imaging | — | aggressive |
| TEST-PET-CT | FDG PET/CT (whole body) | Standard | imaging | — | all tracks |
| TEST-SEZARY-COUNT | Sézary cell count | Standard | lab | CSD Lab ✓ (code TBC) | all tracks |
| TEST-TCR-CLONALITY | TCR clonality | Standard | molecular | CSD Lab ✓ (code TBC) | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- MF with large-cell transformation (LCT — ≥25% large cells on biopsy review) — aggressive variant; mandates systemic therapy reassessment, brentuximab vedotin if CD30+RF-MF-LARGE-CELL-TRANSFORMATION
- MF with B2 blood involvement (Sézary cell count ≥1000/μL OR ≥5% Sézary by morphology) — defines Sézary syndrome / IVA1 stage; routes to systemic therapy with mogamulizumab preferenceRF-MF-SEZARY-LEUKEMIC
- T-cell lymphoma with CD30 expression ≥10% by IHC — qualifies for brentuximab vedotin-based regimen (CHP-Bv per ECHELON-2)RF-TCELL-CD30-POSITIVE
CONTRA-AGGRESSIVE
Hard contraindications to escalation
- Severe pre-existing peripheral neuropathy is an absolute contraindication to bortezomib — therapy will likely worsen the neuropathy to a disabling and often permanent extent.CI-BORTEZOMIB-SEVERE-NEUROPATHY
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-MF-EARLY-1L-SKIN-DIRECTED)
- Do not start systemic chemotherapy in IA-IIA — does not prolong OS, adds toxicity + loses options for progression.
- Do not skip Sezary count + TCR clonality in blood — occult B2 upstages, contraindicates skin-directed alone.
- Do not use NBUVB with photosensitivity (lupus, porphyria) — use topical alternatives.
- Do not forget about skin-cancer screening — MF + skin-directed elevates BCC/SCC risk lifelong.
- Do not interpret progression as failure — restage TNMB; change in T+N+M+B may give a different link to systemic therapy.
Standard plan (IND-MF-ADVANCED-1L-MOGA)
- Do not start mogamulizumab if allo-SCT is planned <50 days — severe GVHD risk per FDA black box.
- Do not ignore drug rash — interrupt + dermatology consult; differentiating from progression is critical.
- Do not combine with other immunosuppressants without dermatology + ID coordination — infection risk elevated.
- Do not use in the absence of MoH-import confirmation or clinical trial — not registered in Ukraine.
- Do not skip Sezary count baseline + repeat q3 mo — primary end point response in B-compartment.
Aggressive plan (IND-MF-ADVANCED-1L-BV)
- Do not prescribe without CD30 IHC ≥10% — ALCANZA inclusion criterion; lower expression = lower response.
- Do not use in pre-existing Grade ≥2 peripheral neuropathy — absolute CI.
- Do not combine with bleomycin (lethal pulmonary toxicity).
- Do not skip neuropathy grading every cycle — dose-cumulative MMAE toxicity.
- Do not use >16 cycles without response justification — risk vs benefit reverses.
Monitoring schedule
Monitoring schedule by treatment phase
Standard plan · MON-MF-SYSTEMIC
| Phase | Window | Tests | Checkpoints |
|---|
| baseline | Within 2 weeks before first dose | TEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH, TEST-SEZARY-COUNT, TEST-TCR-CLONALITY, TEST-FLOW-CYTOMETRY, TEST-CD20-IHC, TEST-HBV-SEROLOGY, TEST-HCV-ANTIBODY, TEST-HIV-SEROLOGY, TEST-PET-CT | - Confirm TNMB stage; document T/N/M/B + IA-IVB stage
- Skin photograph baseline (mSWAT score) for response tracking
- If allo-SCT planned downstream — defer mogamulizumab (severe GVHD risk per FDA black box)
- Dermatology partnership for AE management (mogamulizumab rash ~25%)
|
| induction | Weekly × 5 doses (mogamulizumab) OR every 3 weeks (BV-mono) | TEST-CBC, TEST-CMP | - Infusion reactions (especially mogamulizumab first dose)
- Skin AE grading (CTCAE) — interrupt if severe rash; differentiate drug rash from disease progression
|
| maintenance | Every 2 weeks (mogamulizumab) OR every 3 weeks (BV-mono) until progression / toxicity | TEST-CBC, TEST-CMP, TEST-LFT | - mSWAT skin response every 2-3 months
- Sézary count repeat at 3 months (mogamulizumab — blood compartment response)
- Neuropathy grading on BV-mono
|
| response_assessment | After 12-16 weeks of therapy | TEST-PET-CT, TEST-SEZARY-COUNT | - Global response per ISCL/EORTC consensus (skin + nodes + viscera + blood)
- Continue if responding; switch line if stable/progressive
|
| follow_up | Every 3 months × 2 years post-treatment, then every 6 months | TEST-CBC, TEST-LFT, TEST-LDH, TEST-SEZARY-COUNT | - Surveillance for relapse + LCT
- Skin cancer screening (CTCL + treatment increases risk)
|
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Baseline
Within 2 weeks before first dose
Induction · Mogamulizumab monotherapy (1.0
14-day cycles × 5 weekly induction + maintenance until progression / toxicity
Response assessment
After 12-16 weeks of therapy
Maintenance
Every 2 weeks (mogamulizumab) OR every 3 weeks (BV-mono) until progression / toxicity
Follow-up
Every 3 months × 2 years post-treatment, then every 6 months
Aggressive plan
Baseline
Within 2 weeks before first dose
Induction · Brentuximab vedotin monotherap
21-day cycles × Up to 16 (per ALCANZA); shorter if CR or limiting toxicity
Response assessment
After 12-16 weeks of therapy
Maintenance
Every 2 weeks (mogamulizumab) OR every 3 weeks (BV-mono) until progression / toxicity
Follow-up
Every 3 months × 2 years post-treatment, then every 6 months
MDT brief
Skills (required) — mandatory virtual specialists (1)
Skills (recommended) — for consideration (2)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
- Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-CD20-CONFIRMATION
skill: pathologistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
Open questions (3, 1 blocking)
BLOCKING OQ-CD20-CONFIRMATION
Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated.
Anti-CD20 therapy is the backbone of most lines of treatment; absence of CD20 expression fully changes the regimen.
→ pathologist
OQ-STAGING-COMPLETE
Has complete staging been done (Lugano + PET/CT or CT)?
Prognosis and track selection depend on stage and tumor burden.
→ radiologist
OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist
Data quality
- Missing critical: cd20_ihc_status, lugano_stage
- Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
- Unevaluated RedFlags: RF-MF-LARGE-CELL-TRANSFORMATION, RF-MF-SEZARY-FRAILTY-AGE, RF-MF-SEZARY-INFECTION-SCREENING, RF-MF-SEZARY-LEUKEMIC, RF-MF-SEZARY-ORGAN-DYSFUNCTION
Skill catalog (3/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)
Experimental options (clinical trials)
Last synced: 2026-05-04 · ctgov.
No active trials matched this scenario in ctgov.
Option availability in Ukraine
Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Standard plan — No regimen components on this track — availability unknown | — unknown | — unknown | ₴-? — verify pathway | not recorded |
| Standard plan Mogamulizumab monotherapy (1.0 mg/kg IV weekly × 5, then q2 weeks) (REG-MOGAMULIZUMAB) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Brentuximab vedotin monotherapy for CD30+ MF/cutaneous ALCL (1.8 mg/kg IV q3 weeks) (REG-BV-MONO-MF) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.