Treatment plan — Nodal Marginal Zone Lymphoma

OpenOnco · DIS-NODAL-MZL · Organ dysfunction (CrCl 25, bili 3.5×ULN)

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OpenOnco · Treatment Plan

Treatment plan — Nodal Marginal Zone Lymphoma

PLAN-VAR-NODAL-MZL-ORGAN-V1 · v1 · 2026-05-12

Patient

VAR-NODAL-MZL-ORGAN · Algorithm: ALGO-NMZL-1L

DiagnosisNodal Marginal Zone Lymphoma

MOH / ICD-10C83.0

ICD-O-39699/3

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-CD20-IHC	BIO definition in KB; no ESCAT BMA entry — verify with clinician

Primary current-line option

Active surveillance (watch-and-wait)

★ DEFAULT

Indication: IND-NMZL-1L-WATCH
Regimen: —
Reason: Primary current-line option selected by ALGO-NMZL-1L at step 3.

Other current-line alternatives (3 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Standard plan

Indication

IND-NMZL-1L-BR

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

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NMZL-1L-HCV-POSITIVE

Regimen

Sofosbuvir/Velpatasvir 12 weeks

Drugs + NSZU

Sofosbuvir/Velpatasvir (DRUG-SOFOSBUVIR-VELPATASVIR) 400/100 mg PO · once daily · PO ⚠ NSZU — not for this indication

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-FL-1L-RCHOP-AGGRESSIVE

Regimen

Rituximab + CHOP (R-CHOP), 6 cycles

Drugs + NSZU

Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 of each 21-day cycle · IV ✓ NSZU covered
Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 750 mg/m² · IV day 1 of each 21-day cycle · IV ⚠ NSZU — not for this indication
Doxorubicin (DRUG-DOXORUBICIN) 50 mg/m² · IV day 1 of each 21-day cycle · IV ⚠ NSZU — not for this indication
Vincristine (DRUG-VINCRISTINE) 1.4 mg/m² (capped at 2 mg total) · IV day 1 of each 21-day cycle · IV ⚠ NSZU — not for this indication
Prednisone (DRUG-PREDNISONE) 100 mg · PO days 1-5 of each 21-day cycle · PO ⚠ NSZU — not for this indication

Supportive care

SUP-PJP-PROPHYLAXIS, SUP-TLS-PROPHYLAXIS, SUP-ANTIEMETIC-PREMED

Hard contraindications

CI-HBV-NO-PROPHYLAXIS, CI-LVEF-LOW-FOR-ANTHRACYCLINE

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-BM-ASPIRATE	Bone Marrow Aspirate	Critical	histology	—	aggressive, standard
TEST-BM-TREPHINE	Bone Marrow Trephine	Critical	histology	—	aggressive, standard
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-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-FISH-PANEL	FISH (Fluorescence In Situ Hybridization)	Critical	genomic	CSD Lab ✓ (code TBC)	aggressive
TEST-FLOW-CYTOMETRY	Flow Cytometry	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-HCV-ANTIBODY	HCV Antibody	Critical	lab	—	aggressive, standard
TEST-HIV-SEROLOGY	HIV Antibody/Antigen	Critical	lab	—	aggressive, standard
TEST-LDH	Lactate Dehydrogenase	Critical	lab	—	all tracks
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	all tracks
TEST-LN-EXCISIONAL-BIOPSY	Excisional LN Biopsy	Critical	histology	—	all tracks
TEST-PREGNANCY	Beta-HCG	Critical	lab	—	aggressive
TEST-B2-MICROGLOBULIN	Beta-2 Microglobulin	Standard	lab	—	aggressive, standard
TEST-ECHO	Echocardiography	Standard	imaging	—	aggressive
TEST-PET-CT	FDG PET/CT (whole body)	Standard	imaging	—	all tracks
TEST-FIB4	FIB-4 Index (Fibrosis-4)	Calculation	clinical_assessment	—	standard

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

Decompensated cirrhosis (Child-Pugh B or C): ascites, encephalopathy, variceal bleeding, or jaundice from cirrhosisRF-DECOMP-CIRRHOSIS
Follicular lymphoma meeting GELF criteria for high tumor burden — any of: nodal mass ≥7 cm; ≥3 nodal sites each ≥3 cm; B-symptoms; splenomegaly below umbilicus; pleural/peritoneal effusion; cytopenia (Hb <10, plt <100K, ANC <1.5K) attributable to lymphoma; LDH >ULN; β2M elevated; rapidly progressive diseaseRF-FL-HIGH-TUMOR-BURDEN-GELF
Follicular lymphoma with clinical features concerning for transformation to aggressive lymphoma (typically DLBCL): rapid disease progression, isolated rapidly-growing nodal mass, sudden LDH rise, new B-symptoms, hypercalcemia, extranodal involvement onsetRF-FL-TRANSFORMATION-SUSPECT

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
Pre-treatment LVEF <50% is an absolute contraindication to anthracycline-containing regimens (R-CHOP, Pola-R-CHP, ABVD, BV-AVD, etc.). Cardiotoxicity from doxorubicin is dose-cumulative and often irreversible; starting with already-impaired function risks acute decompensation.CI-LVEF-LOW-FOR-ANTHRACYCLINE

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Active surveillance (watch-and-wait) (IND-NMZL-1L-WATCH)

Do not treat asymptomatic NMZL without GELF-like criteria — as for FL.
Do not skip CD20 + flow + LN biopsy for accurate differentiation from FL/MCL/CLL.
Do not skip re-biopsy for rapidly-growing dominant lesion — transformation requires R-CHOP.

Standard plan (IND-NMZL-1L-BR)

Do not initiate without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+.
Do not use full-dose bendamustine at FIB-4 > 3.25.
Do not skip PJP prophylaxis.
Do not skip re-biopsy on suspicion of transformation — requires R-CHOP.

Standard plan (IND-NMZL-1L-HCV-POSITIVE)

Do not skip HCV testing in all patients with NMZL — DAA may avoid chemoimmunotherapy even for nodal form.
Do not combine sofosbuvir with amiodarone — risk of severe bradycardia.
Do not skip HBV serology before start — occult reactivation possible (RF-UNIVERSAL-HBV-REACTIVATION-RISK).
Do not assess lymphoma response earlier than 6 months after SVR12.
Do not give DAA in decompensated cirrhosis (Child-Pugh B/C) without hepatology consultation.

Aggressive plan (IND-FL-1L-RCHOP-AGGRESSIVE)

Do not prescribe without re-biopsy when transformation is suspected — accurate histology determines treatment.
Do not prescribe without baseline LVEF ≥50% — anthracycline cardiotoxicity.
Do not start without HBV screening + entecavir prophylaxis in HBsAg+ or anti-HBc+.
Do not administer vincristine intrathecally — FATAL.

Monitoring schedule

Monitoring schedule by treatment phase

Standard 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	—

Aggressive plan · MON-R-CHOP-REGIMEN

Phase	Window	Tests	Checkpoints
baseline	Within 2 weeks before cycle 1	TEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH, TEST-B2-MICROGLOBULIN, TEST-HBV-SEROLOGY, TEST-HCV-ANTIBODY, TEST-HIV-SEROLOGY, TEST-PET-CT, TEST-LN-EXCISIONAL-BIOPSY, TEST-FLOW-CYTOMETRY, TEST-CD20-IHC, TEST-ECHO, TEST-PREGNANCY, TEST-BM-ASPIRATE, TEST-BM-TREPHINE	Confirm CD20+ DLBCL histology; rule out double-hit (FISH for MYC/BCL2/BCL6) Confirm HBV status + entecavir prophylaxis plan if HBsAg+ or anti-HBc+ Baseline LVEF ≥50% before doxorubicin IPI calculation documented (age, ECOG, LDH, stage, extranodal sites) CNS-IPI calculation if anatomic risk sites or composite score concerning Fertility preservation discussion (sperm banking / oocyte cryo) for childbearing-age
on_treatment	Day 1 of every 21-day cycle	TEST-CBC, TEST-CMP, TEST-LFT	ANC ≥1500 + platelets ≥100K before each cycle (delay or G-CSF if not) Neuropathy grade documented (CTCAE) — vincristine modification if ≥2 LVEF re-check after cumulative doxorubicin ~300 mg/m²
interim_response_assessment	After cycles 2-4 (interim PET-CT)	TEST-PET-CT, TEST-LDH	Lugano response criteria + Deauville score If Deauville 4-5 with mass progression → consider salvage or trial
end_of_treatment	After cycle 6 (within 6-8 weeks)	TEST-PET-CT, TEST-CBC, TEST-CMP, TEST-LDH	Confirm CR vs PR vs SD vs PD by Lugano/Deauville Begin survivorship plan: cardiac surveillance schedule, vaccination catch-up, second-cancer screening
follow_up_short	Every 3 months × 2 years post-treatment	TEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH	Surveillance for relapse (~40% relapse risk by 2 years overall) HBV reactivation monitoring continues for 12 months post anti-CD20
follow_up_long	Every 6 months years 3-5, then annually	TEST-CBC, TEST-LFT, TEST-ECHO	Late cardiomyopathy screening (LVEF) annually if cumulative dox >300 Annual second-malignancy screening (skin, breast, etc. age-appropriate)

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard 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)

Aggressive plan

Baseline

Within 2 weeks before cycle 1

Induction · Rituximab + CHOP (R-CHOP), 6 cycles

21-day cycles × 6 (with consideration of 2-month interim PET-CT after cycles 2-4)

Response assessment

After cycles 2-4 (interim PET-CT)

Follow-up

Every 3 months × 2 years post-treatment

MDT brief

Discussion questions (4, 1 blocking)

BLOCKING OQ-CD20-CONFIRMATION
Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated.
Anti-CD20 therapy is the backbone of most lines of treatment; absence of CD20 expression fully changes the regimen.
→ pathologist
OQ-STAGING-COMPLETE
Has complete staging been done (Lugano + PET/CT or CT)?
Prognosis and track selection depend on stage and tumor burden.
→ radiologist
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
OQ-BIOMARKER-FL-FLIPI
What is the status of Follicular Lymphoma International Prognostic Index (FLIPI) (BIO-FL-FLIPI)? It is required by track(s): IND-FL-1L-RCHOP-AGGRESSIVE. Expected value: FLIPI 3-5 (high-risk) typically supports R-CHOP intensification over BR; required risk stratifier.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ medical_oncologist

MDT talk tree (5 steps)

#	Owner	Topic	Action
1	pathologist	Pathology confirmation BLOCKING	Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated.
2	hematologist	Staging / disease burden	What is the current LDH? Marker of tumor burden and transformation.
3	medical_oncologist	Biomarker status	What is the status of Follicular Lymphoma International Prognostic Index (FLIPI) (BIO-FL-FLIPI)? It is required by track(s): IND-FL-1L-RCHOP-AGGRESSIVE. Expected value: FLIPI 3-5 (high-risk) typically supports R-CHOP intensification over BR; required risk stratifier.
4	radiologist	Staging / disease burden	Has complete staging been done (Lugano + PET/CT or CT)?
5	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (required) — mandatory virtual specialists (1)

Hematologist / oncohematologist required
Lymphoma diagnosis — leading specialty for treatment management.
Owns: OQ-LDH-CURRENT

Skills (recommended) — for consideration (2)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-CD20-CONFIRMATION

Skills (optional) (1)

Radiation oncologist optional
Extranodal MALT lymphoma — local radiotherapy is an option in certain sites.

Data quality

Incomplete for MDT sign-off. MDT sign-off is incomplete until critical clinical data gaps are resolved.

Biomarker coverage: 3/4 known (75%), 1 missing, 0 default-track gaps
Missing critical: cd20_ihc_status, lugano_stage
Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
Unevaluated RedFlags: RF-NMZL-FRAILTY-AGE, RF-NMZL-HIGH-RISK-BIOLOGY, RF-NMZL-TRANSFORMATION-PROGRESSION

Missing data for doctor action

Priority	Clinical item	Owner	Why it matters	Next action	Blocks
CRITICAL	CD20 IHC status `cd20_ihc_status`	pathologist	Confirms CD20-directed therapy is biologically appropriate.	Verify CD20 IHC result, specimen, method, and report date.	-
CRITICAL	Lugano stage `lugano_stage`	radiologist	Defines lymphoma extent and supports tumor-burden and response-assessment decisions.	Document Lugano stage from PET/CT or contrast CT staging.	-
RECOMMENDED	LDH ratio to ULN `ldh_ratio_to_uln`	medical_oncologist	Supports prognostic scoring and aggressive-biology flags.	Enter LDH with local upper limit of normal.	-
RECOMMENDED	FIB-4 liver fibrosis index `fib4_index`	infectious_disease_hepatology	Screens hepatic fibrosis risk before hepatotoxic therapy or antiviral coordination.	Calculate FIB-4 from age, AST, ALT, and platelet count.	-
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.	-

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-FL-FLIPI`	Follicular Lymphoma International Prognostic Index (FLIPI)	medical_oncologist	no	IND-FL-1L-RCHOP-AGGRESSIVE	Verify result, method, specimen, and report date before sign-off. Expected/constraint: FLIPI 3-5 (high-risk) typically supports R-CHOP intensification over BR; required risk stratifier

Technical MDT skill metadata (4/16 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-ARCAINI-2014: The IELSG-19 randomized trial of MALT lymphoma — chlorambucil + rituximab vs each as monotherapy (2013 final / 2017 long-term follow-up)
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-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)

Experimental options (clinical trials)

Last synced: 2026-05-12 · 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
Active surveillance (watch-and-wait) — No regimen components on this track — availability unknown	— unknown	— unknown	₴-? — verify pathway	not recorded
Standard 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	NSZU formulary
Aggressive plan Rituximab + CHOP (R-CHOP), 6 cycles (REG-R-CHOP)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-12.

plan_id: PLAN-VAR-NODAL-MZL-ORGAN-V1 | version: 1 | generated: 2026-05-12T18:41:26.587699+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.