Patient
VAR-CLL-HBV · Algorithm: ALGO-CLL-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 |
|---|
| No clinically actionable variants matched in this profile. |
| Biomarker | Status |
|---|
| BIO-CD5-IHC | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
| BIO-CD23-IHC | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
| BIO-NOTCH1-MUTATION | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
Primary current-line option
- Indication
- IND-CLL-1L-BTKI
- Regimen
- Acalabrutinib monotherapy (continuous, until progression or intolerance)
- Drugs + NSZU
- Acalabrutinib (DRUG-ACALABRUTINIB) 100 mg · PO twice daily continuous · PO ⚠ NSZU — not for this indication
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS
- Reason
- Primary current-line option selected by ALGO-CLL-1L at step 3.
Other current-line alternatives (3 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-CLL-1L-VENO
- Regimen
- Venetoclax + Obinutuzumab (VenO), 12 months fixed-duration (CLL14 schedule)
- Drugs + NSZU
- Obinutuzumab (DRUG-OBINUTUZUMAB) 100 mg cycle 1 day 1; 900 mg day 2; 1000 mg days 8 + 15; then 1000 mg day 1 of cycles 2-6 · IV monthly (28-day cycles), 6 cycles total · IV ✓ NSZU covered
- Venetoclax (DRUG-VENETOCLAX) 5-week ramp starting cycle 1 day 22: 20 → 50 → 100 → 200 → 400 mg PO daily, then 400 mg daily continuous through cycle 12
· PO daily, total 12 months from start of ramp · PO ✓ NSZU covered
- Allopurinol (DRUG-ALLOPURINOL) 300 mg PO daily · Start 72h before venetoclax ramp; continue ≥1 week post highest dose · PO ⚠ NSZU — not for this indication
- Supportive care
- SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CLL-1L-ZANUBRUTINIB
- Regimen
- Zanubrutinib monotherapy (continuous, ALPINE-style)
- Drugs + NSZU
- Zanubrutinib (DRUG-ZANUBRUTINIB) 160 mg PO twice daily OR 320 mg PO once daily · Continuous until progression or unacceptable toxicity · PO ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CLL-1L-AVO
- Regimen
- Acalabrutinib + Venetoclax + Obinutuzumab (AVO), fixed-duration 14 cycles (AMPLIFY)
- Drugs + NSZU
- Acalabrutinib (DRUG-ACALABRUTINIB) 100 mg PO BID · Continuous twice daily, cycles 1-14 (entire duration) · PO ⚠ NSZU — not for this indication
- Venetoclax (DRUG-VENETOCLAX) 5-week ramp-up starting cycle 3 day 1: week 1 20 mg → week 2 50 mg → week 3 100 mg → week 4 200 mg → week 5 400 mg; then 400 mg QD maintenance through cycle 14
· PO daily, cycles 3-14 (ramp begins cycle 3 day 1) · PO ✓ NSZU covered
- Obinutuzumab (DRUG-OBINUTUZUMAB) Cycle 2 day 1: 100 mg IV; cycle 2 day 2: 900 mg IV; cycle 2 days 8+15: 1000 mg IV; cycles 3-7 day 1: 1000 mg IV
· IV monthly (28-day cycles), cycles 2-7 (6 cycles total) · IV ✓ NSZU covered
- Supportive care
- SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS
- 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-CECT-CAP | CECT chest/abdomen/pelvis | Critical | imaging | — | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-FISH-PANEL | FISH (Fluorescence In Situ Hybridization) | Critical | genomic | 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-B2-MICROGLOBULIN | Beta-2 Microglobulin | Standard | lab | — | all tracks |
| TEST-ECHO | Echocardiography | Standard | imaging | — | all tracks |
| TEST-IMMUNOGLOBULINS | Quantitative Immunoglobulins | Standard | lab | — | all tracks |
| TEST-URIC-ACID | Serum Uric Acid | Standard | lab | — | aggressive |
| TEST-NGS-LYMPHOID-PANEL | Lymphoid NGS Panel | Desired | genomic | CSD Lab ✓ (code TBC) | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Fit performance status (ECOG 0-1): patient is fully active or restricted in physically strenuous activity but ambulatory and able to carry out light work. Eligible for full-dose chemotherapy and intensive regimens (CHOEP, BEACOPP-escalated, HD-MTX, ASCT consolidation, CAR-T).
RF-FITNESS-ECOG-FIT
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
- 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
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-CLL-1L-BTKI)
- Do not prescribe chemoimmuno (FCR / BR) in high-risk CLL — survival impact substantial.
- Do not start ibrutinib instead of acalabrutinib without justification — ELEVATE-RR showed better safety of acalabrutinib.
- Do not skip baseline ECG + cardiology evaluation in atrial fibrillation history or HTN.
- Do not combine BTKi with warfarin without strict monitoring — bleeding risk.
- Do not treat asymptomatic CLL without iwCLL indication — surveillance is the standard.
Aggressive plan (IND-CLL-1L-VENO)
- Do NOT skip the venetoclax 5-week ramp-up — fatal TLS documented.
- Do NOT prescribe with concomitant strong CYP3A4 inhibitor during ramp-up — fatal concentration increase.
- Do NOT start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ (anti-CD20 reactivation).
- Do NOT skip TLS prophylaxis (allopurinol + hydration) — especially with ALC >25K or bulky disease.
- Do NOT do ramp-up on an outpatient with high-burden disease — hospitalization with q6-8h labs required.
- Do NOT forget PJP prophylaxis on prolonged obinutuzumab therapy.
Standard plan (IND-CLL-1L-ZANUBRUTINIB)
- Do not prescribe ibrutinib instead of zanubrutinib without justification — ALPINE / ELEVATE-RR showed better safety of 2nd-gen BTKis.
- Do not skip baseline ECG + cardiology evaluation in atrial fibrillation history or HTN.
- Do not combine with warfarin without strict monitoring — bleeding risk (although lower than ibrutinib).
- Do not treat asymptomatic CLL without iwCLL indication — surveillance is the standard.
- Do not prescribe chemoimmuno (FCR / BR) in TP53-mut or del(17p) — survival impact substantial; BTKi is mandatory.
- Do not skip hold ≥3-7 days pre-major surgery — bleeding risk.
- Do NOT confirm the plan without funding pathway — zanubrutinib is NOT NSZU-reimbursed; ibrutinib (reimbursed) is fallback.
Monitoring schedule
Monitoring schedule by treatment phase
Standard plan · MON-CLL-BTKI
| Phase | Window | Tests | Checkpoints |
|---|
| baseline | Within 2 weeks before start | TEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH, TEST-B2-MICROGLOBULIN, TEST-FISH-PANEL, TEST-NGS-LYMPHOID-PANEL, TEST-IMMUNOGLOBULINS, TEST-HBV-SEROLOGY, TEST-HCV-ANTIBODY, TEST-HIV-SEROLOGY, TEST-CECT-CAP, TEST-ECHO | - Confirm CLL diagnosis: CD19+ CD5+ CD23+ flow on PB ≥5K monoclonal B-cells
- Risk stratification: del(17p), TP53, IGHV mutational status, karyotype
- iwCLL treatment indication documented (if asymptomatic — defer to surveillance)
- Cardiac baseline (atrial fibrillation history, hypertension control)
- HBV status + entecavir prophylaxis if HBsAg+ or anti-HBc+ (anti-CD20 in VenO regimen)
|
| on_treatment_btki | Monthly × 3 months, then every 3 months | TEST-CBC, TEST-CMP, TEST-LFT | - ALC trend (lymphocytosis early on BTKi is expected — not progression)
- Bleeding events; major bleed → hold BTKi
- AF symptoms → ECG; if AF → cardiology + anticoagulation strategy
|
| on_treatment_veno | Per CLL14 schedule during 12-month VenO course | TEST-CBC, TEST-CMP, TEST-LFT, TEST-URIC-ACID | - TLS labs (K+, phosphate, calcium, uric acid, creatinine) per ramp-up schedule
- ANC + platelets pre each obinutuzumab dose
- Infusion reactions to obinutuzumab (especially first dose)
|
| response_assessment | After cycle 6 (VenO) or every 6 months on BTKi | TEST-CBC, TEST-CECT-CAP, TEST-FLOW-CYTOMETRY | - iwCLL response criteria (CR, PR, PR-L on BTKi, SD, PD)
- MRD assessment by flow on PB at end of VenO 12-month course
|
| follow_up | Every 3-6 months after treatment / continuously on BTKi | TEST-CBC, TEST-CMP, TEST-LFT | - Surveillance for relapse (median PFS years for both regimens)
- Watch for Richter transformation (rapid LDH rise, new B-symptoms, isolated mass) — re-biopsy
- Second primary malignancy screening
|
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Baseline
Within 2 weeks before start
Induction · Acalabrutinib monotherapy (continuous, until progression or intolerance)
28-day cycles × Continuous until progression or intolerance
Response assessment
After cycle 6 (VenO) or every 6 months on BTKi
Follow-up
Every 3-6 months after treatment / continuously on BTKi
Aggressive plan
Baseline
Within 2 weeks before start
Induction · Venetoclax + Obinutuzumab (VenO), 12 months fixed-duration (CLL14 schedule)
28-day cycles × 6 obinutuzumab + 12 months total venetoclax
Response assessment
After cycle 6 (VenO) or every 6 months on BTKi
Follow-up
Every 3-6 months after treatment / continuously on BTKi
Standard plan
Baseline
Within 2 weeks before start
Induction · Zanubrutinib monotherapy (continuous, ALPINE-style)
28-day cycles × Continuous
Response assessment
After cycle 6 (VenO) or every 6 months on BTKi
Follow-up
Every 3-6 months after treatment / continuously on BTKi
Aggressive plan
Baseline
Within 2 weeks before start
Induction · Acalabrutinib + Venetoclax + Obinutuzumab (AVO), fixed-duration 14 cycles (AMPLIFY)
28-day cycles × 14 (fixed-duration)
Response assessment
After cycle 6 (VenO) or every 6 months on BTKi
Follow-up
Every 3-6 months after treatment / continuously on BTKi
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (4 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 | infectious_disease_hepatology | Specialist review | Active viral etiology (HCV/HBV) requires parallel antiviral management and reactivation risk assessment. |
| 4 | molecular_geneticist | Specialist review | Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed. |
Skills (recommended) — for consideration (3)
- 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.
- Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
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: 3/3 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-BINET-A, RF-BINET-B-C, RF-CLL-FRAILTY-AGE, RF-CLL-HIGH-RISK, RF-CLL-INFECTION-SCREENING, RF-CLL-ORGAN-DYSFUNCTION, RF-CLL-POST-BTKI-C481-ACTIONABLE, RF-CLL-TP53-DELETION-ACTIONABLE, RF-CLL-TRANSFORMATION-PROGRESSION, RF-CLL-VEN-RESISTANT-ACTIONABLE, RF-RAI-HIGH, RF-RAI-LOW, RF-RICHTER-TRANSFORMATION
Technical MDT skill metadata (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-CLL14-FISCHER-2019: Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions (2019)
- SRC-ELEVATE-TN-SHARMAN-2020: Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN) (2020)
- SRC-ESMO-CLL-2024: ESMO Clinical Practice Guideline on Chronic Lymphocytic Leukaemia (2024)
- SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)
Experimental options (clinical trials)
Last synced: 2026-05-13 · 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 Acalabrutinib monotherapy (continuous, until progression or intolerance) (REG-ACALABRUTINIB-CONTINUOUS) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Venetoclax + Obinutuzumab (VenO), 12 months fixed-duration (CLL14 schedule) (REG-VENETOCLAX-OBINUTUZUMAB) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Zanubrutinib monotherapy (continuous, ALPINE-style) (REG-ZANUBRUTINIB-CONTINUOUS) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Acalabrutinib + Venetoclax + Obinutuzumab (AVO), fixed-duration 14 cycles (AMPLIFY) (REG-AVO-CLL-1L) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-13.