Treatment plan — DIS-CLL

OpenOnco · Treatment Plan

PLAN-CLL-LOWRISK-001-V1 · v1 · 2026-04-27

Patient

CLL-LOWRISK-001 · Algorithm: ALGO-CLL-1L

Clinical significance of mutations (ESCAT / OncoKB)

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

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

Treatment options (2 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

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Needed for
TEST-CBC	Загальний аналіз крові з лейкоцитарною формулою	Critical	lab	all tracks
TEST-CECT-CAP	КТ органів грудної клітки/черевної порожнини/таза з внутрішньовенним контрастуванням	Critical	imaging	all tracks
TEST-CMP	Розширений біохімічний аналіз крові	Critical	lab	all tracks
TEST-FISH-PANEL	FISH-панель (специфічна для нозології)	Critical	genomic	all tracks
TEST-HBV-SEROLOGY	Серологія HBV: HBsAg, anti-HBc, anti-HBs	Critical	lab	all tracks
TEST-HCV-ANTIBODY	Антитіла до HCV	Critical	lab	all tracks
TEST-HIV-SEROLOGY	Серологія ВІЛ (антитіла HIV-1/2 + p24)	Critical	lab	all tracks
TEST-LDH	Лактатдегідрогеназа (ЛДГ)	Critical	lab	all tracks
TEST-LFT	Печінкові проби (АЛТ, АСТ, білірубін, ЛФ, ГГТП, альбумін)	Critical	lab	all tracks
TEST-B2-MICROGLOBULIN	Бета-2-мікроглобулін	Standard	lab	all tracks
TEST-ECHO	Ехокардіографія (ТТЕ) з оцінкою ФВ ЛШ	Standard	imaging	all tracks
TEST-IMMUNOGLOBULINS	Кількісні імуноглобуліни (IgG, IgA, IgM)	Standard	lab	all tracks
TEST-URIC-ACID	Сечова кислота сироватки	Standard	lab	aggressive
TEST-NGS-LYMPHOID-PANEL	NGS-панель лімфоїдних мутацій	Desired	genomic	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)

Не призначати chemoimmuno (FCR / BR) при високоризиковій ХЛЛ — survival impact substantial.
Не починати ibrutinib замість acalabrutinib без обґрунтування — ELEVATE-RR показав кращу безпеку акалабрутинібу.
Не пропускати baseline ECG + кардіологічну оцінку при atrial fibrillation history або HTN.
Не комбінувати BTKi із warfarin без strict monitoring — ризик кровотечі.
Не лікувати asymptomatic CLL без iwCLL індикації — surveillance є стандартом.

Aggressive plan (IND-CLL-1L-VENO)

НЕ skip-ити venetoclax 5-week ramp-up — летальний TLS зафіксовано.
НЕ призначати при concomitant strong CYP3A4 inhibitor під час ramp-up — летальне підвищення концентрації.
НЕ починати без HBV скринінгу + entecavir prophylaxis при HBsAg+ або anti-HBc+ (anti-CD20 reactivation).
НЕ пропускати TLS prophylaxis (allopurinol + hydration) — особливо при ALC >25K або bulky disease.
НЕ робити ramp-up на amбулаторного пацієнта при high-burden disease — потрібна госпіталізація з q6-8h labs.
НЕ забути PJP prophylaxis на тривалу терапію obinutuzumab.

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

MDT brief

Skills (recommended) — for consideration (2)

Клінічний фармацевт recommended
Хіміоімунотерапевтичний схема — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
Молекулярний генетик / молекулярний онколог recommended
Indication посилається на actionable геномний біомаркер — потрібна інтерпретація мутації / target / actionability.
skill: molecular_geneticistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

OQ-LDH-CURRENT
Який актуальний LDH? Маркер пухлинного навантаження і трансформації.
LDH входить у прогностичні індекси індолентних лімфом.
→ 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
Specialist з клітинної терапії (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Клінічний фармацевт	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Гематолог / онкогематолог	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Гематопатолог (специфічно для лімфом / лейкозів / мієломи)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Інфекціоніст / гепатолог	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Медичний онколог (хіміотерапевт солідних пухлин)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Молекулярний генетик / молекулярний онколог	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Паліативна допомога	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Патолог (загальний)	`pathologist`	v0.1.0	2026-04-25	pathology
Сімейний лікар / терапевт	`primary_care`	v0.1.0	2026-04-25	primary_care
Психолог / онкопсихолог	`psychologist`	v0.1.0	2026-04-25	psychosocial
Радіотерапевт (променева терапія)	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Лікар-радіолог	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Соціальний працівник / кейс-менеджер	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Хірург-онколог	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Specialist з трансплантації (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)

Експериментальні опції (клінічні дослідження)

Третій трек плану — open-enrollment trials з ClinicalTrials.gov. Останнє оновлення: 2026-04-26. Render-time metadata; engine selection не змінюється цим блоком (CHARTER §8.3).

NCT	Name	Phase	Статус	Спонсор	UA
NCT06708897	A Phase 1 Study of ZE50-0134 in Relapsed and Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Select Low-grad Lymphomas	PHASE1	RECRUITING	Lomond Therapeutics Holdings, Inc.	—
NCT05371808	Economic Analysis of Early vs Delayed Therapy in Newly Diagnosed Asymptomatic High-Risk Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma:	N/A	RECRUITING	Canadian Cancer Trials Group	—
NCT06508684	Current Status of BTKi Treatment for CLL/SLL in China	N/A	RECRUITING	The First Affiliated Hospital with Nanjing Medical University	—
NCT05602363	AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma	PHASE1	RECRUITING	Carna Biosciences, Inc.	—
NCT04771572	Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory CLL, SLL, MDS, MDS/MPN, AML, CMML-2, MPN-BP, ALL, MF, NHL, RT, MM or T-PLL.	PHASE1	RECRUITING	Newave Pharmaceutical Inc	—
NCT05643742	A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies	PHASE1 / PHASE2	RECRUITING	CRISPR Therapeutics AG	—
NCT03824483	Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL)	PHASE2	RECRUITING	Memorial Sloan Kettering 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.	—
NCT04588922	Study of SLS009 (Formerly GFH009) a Potent Highly Selective CDK9 Inhibitor in Patients With Hematologic Malignancies and High-Risk Newly Diagnosed AML	PHASE1 / PHASE2	RECRUITING	Sellas Life Sciences Group	—
NCT07139873	A Study of DZD8586 Versus Investigator's Choice in r/r CLL/SLL (TAI-SHAN6)	PHASE3	RECRUITING	Dizal (Jiangsu) Pharmaceutical Co., Ltd.	—

Перевіряти статус набору безпосередньо у дослідницькому центрі. Дані ctgov можуть відставати від поточного статусу UA-сайтів.

Доступність опцій в Україні

Per-track UA registration · НСЗУ · cost · access pathway. Render-time metadata; engine selection не залежить від цих полів (CHARTER §8.3).

Опція	Реєстрація UA	НСЗУ	Cost orientation	Access pathway
Standard plan Acalabrutinib monotherapy (continuous, until progression or intolerance) (REG-ACALABRUTINIB-CONTINUOUS)	✓ зареєстровано	✓ покривається	₴-? — verify pathway	НСЗУ formulary
Aggressive plan Venetoclax + Obinutuzumab (VenO), 12 months fixed-duration (CLL14 schedule) (REG-VENETOCLAX-OBINUTUZUMAB)	✓ зареєстровано	✓ покривається	₴-? — verify pathway	НСЗУ formulary
Trial · NCT06708897 A Phase 1 Study of ZE50-0134 in Relapsed and Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Select Low-grad Lymphomas No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT05371808 Economic Analysis of Early vs Delayed Therapy in Newly Diagnosed Asymptomatic High-Risk Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT06508684 Current Status of BTKi Treatment for CLL/SLL in China No UA site listed — international referral required	— невідомо	— невідомо	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	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT04771572 Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory CLL, SLL, MDS, MDS/MPN, AML, CMML-2, MPN-BP, ALL, MF, NHL, RT, MM or T-PLL. No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT05643742 A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT03824483 Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL) No UA site listed — international referral required	— невідомо	— невідомо	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	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT04588922 Study of SLS009 (Formerly GFH009) a Potent Highly Selective CDK9 Inhibitor in Patients With Hematologic Malignancies and High-Risk Newly Diagnosed AML No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT07139873 A Study of DZD8586 Versus Investigator's Choice in r/r CLL/SLL (TAI-SHAN6) No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor

Інформація про ціни — orientation. Перевіряти у конкретній аптеці / foundation / трайл-сайті. Status updated: 2026-04-27.

plan_id: PLAN-CLL-LOWRISK-001-V1 | version: 1 | generated: 2026-04-27T10:14:01.348786+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.