Patient
PV-2L-RUX-001 · Algorithm: ALGO-PV-2L
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-JAK2 | V617F (exon 14, JH2 pseudokinase domain — present in ~95% of polycythemia vera) | IA | Molecular evidence option Trial or research option - SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| JAK2 V617F is the defining driver of polycythemia vera (~95%) and a WHO 2022 / ICC 2022 major diagnostic criterion (per SRC-NCCN-MPN-2025, SRC-ESMO-MPN-2015). Treatment is risk-stratified, not variant-genotype directed: low-risk PV → phlebotomy + low-dose aspirin; high-risk PV (age ≥60 or prior thrombosis) → cytoreduction with hydroxyurea or interferon-alpha (ropeginterferon-alfa-2b, PROUD-PV / CONTINUATION-PV Gisslinger 2020 — superior molecular response and event-free survival at 5y vs hydroxyurea); ruxolitinib (RESPONSE Vannucchi 2015 — 21% CHR + spleen response vs 1% best available therapy) for hydroxyurea- intolerant or -resistant disease. | phlebotomy + low-dose aspirin (low-risk PV per SRC-NCCN-MPN-2025)
hydroxyurea (high-risk 1L cytoreduction per SRC-NCCN-MPN-2025, SRC-ESMO-MPN-2015)
ropeginterferon alfa-2b (high-risk; preferred for younger patients per SRC-PROUD-PV-GISSLINGER-2020)
ruxolitinib (post-hydroxyurea resistance/intolerance per SRC-RESPONSE-VANNUCCHI-2015) | - SRC-NCCN-MPN-2025
- SRC-ESMO-MPN-2015
- SRC-RESPONSE-VANNUCCHI-2015
- SRC-PROUD-PV-GISSLINGER-2020
|
Primary current-line option
- Indication
- IND-PV-2L-RUXOLITINIB
- Regimen
- Ruxolitinib (PV — HU-resistant / intolerant)
- Drugs + NSZU
- Ruxolitinib (DRUG-RUXOLITINIB) 10 mg PO BID — start; titrate to Hct <45% + WBC + plt control (max 25 mg BID) · continuous PO twice daily; do NOT abrupt-stop (cytokine rebound) · PO ✓ NSZU covered
- Aspirin (DRUG-ASPIRIN) 81-100 mg PO daily · continuous · PO ⚠ Out-of-pocket
- Supportive care
- SUP-HBV-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS
- Reason
- Primary current-line option selected by ALGO-PV-2L at step 4.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-PV-1L-ROPEGINTERFERON
- Regimen
- Ropeginterferon alfa-2b (Besremi) for PV — 1L cytoreductive
- Drugs + NSZU
- Ropeginterferon alfa-2b (DRUG-ROPEGINTERFERON-ALFA-2B) Initial 100 µg SC every 2 weeks (50 µg if HU co-administered); titrate by 50 µg q2wk based on response + tolerance to maximum 500 µg q2wk · Q2wk continuous; may extend to q4wk after sustained hematologic response ≥1 year; continue indefinitely · SC ✗ Not registered in UA
- Aspirin (DRUG-ASPIRIN) 81-100 mg PO daily · Continuous lifelong · PO ⚠ Out-of-pocket
- Reason
- Current-line alternative 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-BCR-ABL-JAK2 | BCR-ABL + JAK2 + CALR + MPL | Critical | genomic | CSD Lab ✓ (code TBC) | all tracks |
| TEST-BM-ASPIRATE | Bone Marrow Aspirate | Critical | histology | — | desired (aggressive) |
| TEST-BM-TREPHINE | Bone Marrow Trephine | Critical | histology | — | desired (aggressive) |
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | 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 | — | desired (aggressive) |
| TEST-IRON-PANEL | Iron Panel | Standard | lab | — | all tracks |
| TEST-RETICULOCYTE | Reticulocyte Count | Standard | lab | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- PV or ET patient elderly or frail (age ≥80, ECOG ≥3, multiple comorbidities, life expectancy <5 years) — gentler cytoreduction (lower HU dose), expanded transfusion + monitoring strategy
Direction "investigate"-equivalent — surfaces dose-attenuation annotation; does not switch indication. Older patients tolerate HU well long-term but the leukemogenic-conversion concern weighs less; choice often defaults to HU 1L…
RF-PV-ET-FRAILTY-AGESRC-NCCN-MPN-2025SRC-ESMO-MPN-2015 - PV or ET patient with organ dysfunction limiting cytoreductive choice: severe renal impairment (CrCl <30 — limits HU), severe hepatic dysfunction (limits ruxolitinib), or severe cardiac dysfunction (limits anagrelide)
Direction "investigate" — surfaces dose-modification / agent-substitution annotations, not a binary indication switch. CrCl <30 → reduce HU dose, monitor for myelosuppression. Hepatic dysfunction → reduce/avoid ruxolitinib (CYP3A4…
RF-PV-ET-ORGAN-DYSFUNCTIONSRC-NCCN-MPN-2025SRC-ESMO-MPN-2015 - PV or ET patient pregnant or planning pregnancy — HU and anagrelide contraindicated; switch to interferon-α (PEG-IFN-α2a or ropeginterferon)
Direction "investigate" — surfaces an agent-substitution annotation. Pregnancy in MPN is high-risk (placental thrombosis, IUGR, miscarriage) and requires hematology + maternal-fetal-medicine co-management. Interferon-α is the…
RF-PV-ET-PREGNANCY-OR-PLANNINGSRC-NCCN-MPN-2025SRC-ESMO-MPN-2015 - PV resistant or intolerant to hydroxyurea per ELN criteria: persistent need for phlebotomy on HU 2 g/day, persistent symptoms, splenomegaly progression, cytopenias at minimum effective HU dose, or HU-related cutaneous ulcers — switch to ruxolitinib (RESPONSE)
RESPONSE trial established ruxolitinib as 2L for HU-resistant / intolerant PV (Hct + spleen-volume composite primary endpoint 21% vs 1%). NOT applicable as 1L (no proven OS benefit over HU). Pegylated interferon-α (ropeginterferon) is…
RF-PV-HU-RESISTANCE-INTOLERANCESRC-NCCN-MPN-2025SRC-RESPONSE-VANNUCCHI-2015
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-PV-2L-RUXOLITINIB)
- Do NOT prescribe without verified HU resistance/intolerance per ELN — slot 2L specific.
- Do NOT discontinue abrupt — taper ≥1-2 weeks; cytokine rebound + spleen flare can be life-threatening.
- Do NOT initiate without HBV / HCV / HIV / TB screening — JAKi may reactivate latent infection.
- Do NOT combine with strong CYP3A4-inhibitor (fluconazole, clarithromycin) without dose reduction ~50%.
- Do NOT ignore zoster prophylaxis in HSV-positive — reactivation documented.
- Do NOT forget aspirin 81-100 mg PO daily for thrombosis prevention (continued from PV pathway).
- Do NOT confirm plan without funding pathway — drug not reimbursed for PV in Ukraine.
Aggressive plan (IND-PV-1L-ROPEGINTERFERON)
- Do NOT prescribe without baseline psychiatric screen (depression, suicidality) — black-box warning, fatal cases documented.
- Do NOT prescribe with decompensated liver disease (Child-Pugh B/C) — autoimmune hepatitis risk.
- Do NOT prescribe with active severe autoimmune disease — exacerbation expected.
- Do NOT ignore baseline TSH + autoantibody panel + serial LFT — autoimmune thyroiditis + hepatitis common.
- Do NOT forget aspirin 81-100 mg PO daily for thrombosis prevention (continued from PV pathway).
- Do NOT continue with severe depression / suicidality — permanent discontinuation.
- Do NOT confirm plan without funding pathway — drug not registered in Ukraine; standard PEG-IFNa-2a (off-label PV) as alternative if available.
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (3 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 3 | social_worker_case_manager | Specialist review | Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed. |
Skills (recommended) — for consideration (2)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.
Data quality
Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.
- Biomarker coverage: 0/0 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-PV-ET-FRAILTY-AGE, RF-PV-ET-HIGH-THROMBOSIS-RISK, RF-PV-ET-INFECTION-SCREENING, RF-PV-ET-ORGAN-DYSFUNCTION, RF-PV-ET-PREGNANCY-OR-PLANNING, RF-PV-HU-RESISTANCE-INTOLERANCE
Technical MDT skill metadata (2/16 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-ESMO-MPN-2015: Philadelphia-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2015)
- SRC-NCCN-MPN-2025: NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms (v.X.2025)
- SRC-PROUD-PV-GISSLINGER-2020: Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study (2020)
- SRC-RESPONSE-VANNUCCHI-2015: Ruxolitinib versus standard therapy for the treatment of polycythemia vera (2015)
Experimental options (clinical trials)
Last synced: 2026-07-26 · 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 |
|---|
| Aggressive plan Ruxolitinib (PV — HU-resistant / intolerant) (REG-RUX-PV) 1/2 component drug(s) not on NSZU formulary | ✓ registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Ropeginterferon alfa-2b (Besremi) for PV — 1L cytoreductive (REG-ROPEGINTERFERON-PV) 1/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-07-26.