Patient
PZ-DIAG-001 · Algorithm: ALGO-HCV-MZL-1L
Etiological driver
Etiological driver · etiologically_driven archetype
HCV-associated Marginal Zone Lymphoma
- Hepatitis C virus (HCV) infection — primary driver
- Chronic antigen stimulation via HCV E2 protein
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-HCV-RNA-QUANTITATIVE-MONITORING | Quantitative HCV RNA — viral-load monitoring during DAA therapy | IIIA | Standard care - SRC-AASLD-IDSA-HCV-2023: Level Class I / Level A
- SRC-EASL-HCV-2023: Level A1
| Quantitative HCV RNA monitoring during direct-acting antiviral (DAA) therapy: pretreatment viral load (baseline), end-of-treatment (EOT), and Sustained Virological Response at 12 weeks (SVR12) are the standard treatment-response milestones (AASLD-IDSA 2023; EASL 2023). SVR12 is the evidence-based cure surrogate. Persistent viraemia after week 4 / EOT or detectable viraemia at SVR12 → relapse; switch to a salvage regimen containing sofosbuvir-velpatasvir-voxilaprevir (POLARIS-1). In HCV-associated MZL, lymphoma-response correlates with virologic response (Arcaini 2014; Hermine 2002); HCV eradication itself is first-line MZL therapy for indolent disease per ESMO MZL 2024. ESCAT IIIA — biomarker directs DAA regimen selection / continuation decisions and (in HCV-MZL) drives the primary cancer-directed therapy. | SVR12-confirmed (cure): no further DAA; surveillance per IND-HCV-MZL-POST-DAA-SURVEILLANCE
Treatment failure / relapse: sofosbuvir + velpatasvir + voxilaprevir (POLARIS-1) salvage | - SRC-EASL-HCV-2023
- SRC-AASLD-IDSA-HCV-2023
|
Primary current-line option
- Indication
- IND-HCV-MZL-1L-BR-AGGRESSIVE
- Regimen
- Bendamustine + Rituximab (BR), 6 cycles
- Drugs + NSZU
- Rituximab (DRUG-RITUXIMAB) 375 mg/m² · day 1 of each 28-day cycle · IV ✓ NSZU covered
- Bendamustine (DRUG-BENDAMUSTINE) 90 mg/m² · days 1 and 2 of each 28-day cycle · IV ⚠ NSZU — not for this indication
- Supportive care
- SUP-ANTIEMETIC-PREMED, SUP-PJP-PROPHYLAXIS
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS, CI-SEVERE-CYTOPENIA-BR
- Reason
- Primary current-line option selected by ALGO-HCV-MZL-1L at step 4.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-HCV-MZL-1L-ANTIVIRAL
- Regimen
- Sofosbuvir/Velpatasvir 12 weeks
- Drugs + NSZU
- Sofosbuvir/Velpatasvir (DRUG-SOFOSBUVIR-VELPATASVIR) 400/100 mg PO · once daily · PO ✓ NSZU covered
- 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-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CD20-IHC | CD20 Immunohistochemistry | 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-LDH | Lactate Dehydrogenase | Critical | lab | — | all tracks |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-PET-CT | FDG PET/CT (whole body) | Standard | imaging | — | aggressive |
| TEST-FIB4 | FIB-4 Index (Fibrosis-4) | Calculation | clinical_assessment | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Histologic evidence of transformation to aggressive large B-cell lymphoma (DLBCL) on biopsy or suspected by rapid clinical progression / LDH elevation / PET hotspotRF-AGGRESSIVE-HISTOLOGY-TRANSFORMATION
- Bulky lymphoma disease: single nodal mass >=7 cm OR mediastinal mass >1/3 thoracic diameter OR significant symptomatic burdenRF-BULKY-DISEASE
CONTRA-AGGRESSIVE
Hard contraindications to escalation
- Active or latent HBV without antiviral prophylaxis is an absolute contraindication to starting B-cell-depleting / immunomodulatory monoclonal antibody therapy (anti-CD20, anti-CD30 ADC, anti-CD38). Severe HBV reactivation hepatitis risk including fulminant hepatic failure.CI-HBV-NO-PROPHYLAXIS
- Severe baseline cytopenia is a relative contraindication to starting bendamustine + rituximab — high risk of profound myelosuppression.CI-SEVERE-CYTOPENIA-BR
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-HCV-MZL-1L-BR-AGGRESSIVE)
- Do not start anti-CD20 therapy without HBV prophylaxis (entecavir) in HBsAg+ or anti-HBc+ — risk of fulminant hepatitis.
- Do not use full-dose bendamustine (90 mg/m²) at FIB-4 > 3.25 or compensated cirrhosis — reduce to 70 mg/m².
- Do not skip PJP prophylaxis (cotrimoxazole) during BR + ≥6 months after the last dose of anti-CD20.
- Do not start the regimen at ANC <1500/µL or platelets <75K — delay the cycle, consider G-CSF support.
- Do not administer bendamustine at CrCl <30 mL/min without dose adjustment — toxicity increases exponentially.
Standard plan (IND-HCV-MZL-1L-ANTIVIRAL)
- Do not add chemoimmunotherapy before evaluating response to DAA at month 6 (premature escalation negates the essence of antiviral-first logic).
- Do not combine sofosbuvir with amiodarone — risk of severe bradycardia and cardiac arrest.
- Do not skip HBV serology (HBsAg + anti-HBc) before start — occult HBV may reactivate even with an antiviral-only approach.
- Do not prescribe DAA in decompensated cirrhosis (Child-Pugh B/C) without a hepatology consult — separate regimen.
- Do not assess lymphoma response earlier than 6 months after SVR12 — remission unfolds slowly.
Monitoring schedule
Monitoring schedule by treatment phase
Aggressive plan · MON-BR-REGIMEN
| Phase | Window | Tests | Checkpoints |
|---|
| baseline | Within 2 weeks before cycle 1 | TEST-CBC, TEST-LFT, TEST-LDH, TEST-HBV-SEROLOGY, TEST-FIB4, TEST-CD20-IHC, TEST-PET-CT | - Confirm CD20+ histology
- Confirm HBV status and prophylaxis plan
- FIB-4 + LFT determine bendamustine dose adjustment
|
| on_treatment | Day 1 of every 28-day cycle | TEST-CBC, TEST-LFT | - ANC ≥ 1500/µL and platelets ≥ 75K before each cycle (delay otherwise)
- ALT/AST trend (rising values may signal HBV reactivation or hepatotoxicity)
|
| response_assessment | After cycles 3 and 6 | TEST-PET-CT, TEST-LDH | - Lugano response criteria (CR, PR, SD, PD)
- If <PR after cycle 3 → consider regimen change
|
| follow_up_short | Every 3 months for 2 years post-treatment | TEST-CBC, TEST-LFT, TEST-LDH | - Surveillance for relapse
- HBV reactivation monitoring continues for 12 months post anti-CD20
|
| follow_up_long | Every 6 months years 3-5 | TEST-CBC, TEST-LFT | — |
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Baseline
Within 2 weeks before cycle 1
Induction · Bendamustine + Rituximab (BR), 6 cycles
28-day cycles × 6
Response assessment
After cycles 3 and 6
Follow-up
Every 3 months for 2 years post-treatment
Standard plan
Induction · Sofosbuvir/Velpatasvir 12 weeks
84-day cycles × 1 (continuous 12-week course)
MDT brief
MDT talk tree (5 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Specialist review | Lymphoma diagnosis — leading specialty for treatment management. |
| 2 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 3 | infectious_disease_hepatology | Specialist review | Active viral etiology (HCV/HBV) requires parallel antiviral management and reactivation risk assessment. |
| 4 | pathologist | Specialist review | Confirm lymphoma histology + assess transformation risk (DLBCL/Richter). |
| 5 | radiologist | Specialist review | Imaging findings present — radiologist needed for staging/restaging. |
Skills (required) — mandatory virtual specialists (1)
Skills (recommended) — for consideration (4)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Infectious disease / hepatology recommended
Active viral etiology (HCV/HBV) requires parallel antiviral management and reactivation risk assessment.
- Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
- Radiologist recommended
Imaging findings present — radiologist needed for staging/restaging.
Skills (optional) (1)
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: 1/1 known (100%), 0 missing, 0 default-track gaps
- Missing recommended: pet_ct_date
- Unevaluated RedFlags: RF-AGGRESSIVE-HISTOLOGY-TRANSFORMATION, RF-BULKY-DISEASE, RF-CHRONIC-HCV-NHL-PREVENTION-OPPORTUNITY, RF-HCV-MZL-FRAILTY-AGE, RF-SJOGREN-MALT-LYMPHOMA-PREVENTION
Missing data for doctor action
| Priority | Clinical item | Owner | Why it matters | Next action | Blocks |
|---|
| RECOMMENDED | PET/CT date pet_ct_date
| radiologist | Shows whether baseline staging is recent enough for treatment planning and later response comparison. | Document baseline PET/CT date or explain alternative staging modality. | - |
Technical MDT skill metadata (6/16 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-EASL-HCV-2023: EASL Clinical Practice Guidelines on Hepatitis C Virus Infection (2023)
- SRC-ESMO-LYMPHOMA-2025: Lymphomas: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up (2025)
- SRC-MOZ-UA-LYMPH-2013: Уnoфікований кліnoчний протокол первинної, вторинної (спеціалізованої) медичної допомоги: Лімфоми (2013-10-30 (Наказ МОЗ України № 866))
- SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)
Experimental options (clinical trials)
Last synced: 2026-06-11 · 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 Bendamustine + Rituximab (BR), 6 cycles (REG-BR-STANDARD) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Sofosbuvir/Velpatasvir 12 weeks (REG-DAA-SOF-VEL) | ✓ registered | ✓ covered | ₴-? — verify pathway | AP-DAA-SOF-VEL-NSZU |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-06-11.