OpenOnco · Treatment Plan

Treatment plan — DIS-CLL

PLAN-BMA-ATM_LOSS_CLL-V1 · v1 · 2026-05-04

Patient

BMA-ATM_LOSS_CLL · Algorithm: ALGO-CLL-1L

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
No clinically actionable variants matched in this profile.

⚠️ Not included in plan

Biomarker	Status
BIO-HRR-PANEL	Not in KB — ask clinician to verify

Treatment options (3 tracks)

Standard plan

★ DEFAULT

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

Engine default per algorithm ALGO-CLL-1L: {'step': 3, 'outcome': False, 'branch': {'result': 'IND-CLL-1L-BTKI'}, 'fired_red_flags': [], 'winner_red_flag': None}

Aggressive plan

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

Alternative track presented for HCP consideration

Standard plan

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

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-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

CLL with high-risk genetics: TP53 mutation OR del(17p) OR IGHV-unmutated OR complex karyotype (≥3 abnormalities)RF-CLL-HIGH-RISK
CLL with del(17p) by FISH AND/OR TP53 mutation by NGS — ~5-10% at diagnosis, rising to ~30-40% in R/R disease. Defines a chemoimmuno- refractory subset (FCR/BR contraindicated; chemo OS <2 years). 1L selection narrows to two targeted-only routes: continuous BTKi (acalabrutinib, zanubrutinib, ibrutinib) OR fixed-duration venetoclax + obinutuzumab (CLL14, Fischer NEJM 2019; del(17p)/TP53-mut subgroup mPFS >5 years). NCCN/ESMO 2024 prefer fixed-duration ven + obinutuzumab over continuous BTKi for patient-preference and cardiac/bleeding-risk profiles, while continuous BTKi preferred for high disease bulk or patients unable to tolerate TLS-prophylaxis ramp. RF-CLL-TP53-DELETION-ACTIONABLE

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

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 (con

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 (Ven

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 (cont

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

MDT brief

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
Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
skill: molecular_geneticistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

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

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

Skill catalog (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	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	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)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-04.

NCT	Title	Phase	Status	Sponsor	UA
NCT06943872	A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL)	PHASE3	RECRUITING	BeOne Medicines	—
NCT05602363	AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma	PHASE1	RECRUITING	Carna Biosciences, Inc.	—
NCT07014917	Intermittent Versus Continuous Venetoclax With Acalabrutinib for CLL/SLL	PHASE2	RECRUITING	Zulfa Omer	—
NCT07221500	A Study of NX-5948 in Adults With CLL/SLL Previously Treated With a Bruton's Tyrosine Kinase Inhibitor and a B-cell Lymphoma-2 Inhibitor (DAYBreak CLL-201)	PHASE2	RECRUITING	Nurix Therapeutics, Inc.	—
NCT06876662	A Study of (LY3527727) Pirtobrutinib in Participants With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Non-Hodgkin Lymphoma	PHASE4	RECRUITING	Eli Lilly and Company	—
NCT04545762	Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma	PHASE1	RECRUITING	C. Babis Andreadis	—
NCT04505254	Acalabrutinib and Obinutuzumab for the Treatment of Chronic Lymphocytic Leukemia	PHASE2	RECRUITING	M.D. Anderson Cancer Center	—
NCT04494503	Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory CLL/SLL	PHASE1 / PHASE2	RECRUITING	Ascentage Pharma Group Inc.	—
NCT06564038	A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies	PHASE1 / PHASE2	RECRUITING	AstraZeneca	—
NCT06958705	Venetoclax as Consolidation in CLL Patients Treated With BTK Inhibitor Monotherapy	PHASE2	RECRUITING	The First Affiliated Hospital with Nanjing Medical University	—

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

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
Trial · NCT06943872 A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05602363 AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07014917 Intermittent Versus Continuous Venetoclax With Acalabrutinib for CLL/SLL No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07221500 A Study of NX-5948 in Adults With CLL/SLL Previously Treated With a Bruton's Tyrosine Kinase Inhibitor and a B-cell Lymphoma-2 Inhibitor (DAYBreak CLL-201) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06876662 A Study of (LY3527727) Pirtobrutinib in Participants With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Non-Hodgkin Lymphoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04545762 Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04505254 Acalabrutinib and Obinutuzumab for the Treatment of Chronic Lymphocytic Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04494503 Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory CLL/SLL No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06564038 A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06958705 Venetoclax as Consolidation in CLL Patients Treated With BTK Inhibitor Monotherapy No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.

plan_id: PLAN-BMA-ATM_LOSS_CLL-V1 | version: 1 | generated: 2026-05-04T14:13:16.583171+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.