OpenOnco · Treatment Plan

Treatment plan — Splenic Marginal Zone Lymphoma

PLAN-VAR-SPLENIC-MZL-RELAPSED-V1 · v1 · 2026-05-13

Patient

VAR-SPLENIC-MZL-RELAPSED · Algorithm: ALGO-SMZL-2L

DiagnosisSplenic Marginal Zone Lymphoma

MOH / ICD-10C83.0

ICD-O-39689/3

Etiological driver

Etiological driver · etiologically_driven archetype

Splenic Marginal Zone Lymphoma

Hepatitis C virus (HCV) infection — etiologically associated in 10-30% (geographic variation)
Splenic localization of marginal zone B-cells
Frequent del(7q) cytogenetic abnormality

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-HCV-STATUS	BIO definition in KB; no ESCAT BMA entry — verify with clinician

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-SMZL-2L-BR

Regimen

R-Bendamustine for relapsed marginal zone lymphoma (post-rituximab failure)

Drugs + NSZU

Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 · IV ✓ NSZU covered
Bendamustine (DRUG-BENDAMUSTINE) 90 mg/m² · IV days 1-2 · IV ⚠ NSZU — not for this indication

Hard contraindications

CI-HBV-NO-PROPHYLAXIS, CI-SEVERE-CYTOPENIA-BR

Reason

Primary current-line option selected by ALGO-SMZL-2L at step 3.

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	—	all tracks
TEST-BM-TREPHINE	Bone Marrow Trephine	Critical	histology	—	all tracks
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-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	—	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

CONTRA-AGGRESSIVE

Hard contraindications to escalation

What NOT to do

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

Standard plan (IND-SMZL-2L-BR)

Do NOT prescribe without HBV screening + prophylaxis if HBsAg+ or anti-HBc+.
Do NOT use full-dose bendamustine at FIB-4 >3.25 — reduce to 70 mg/m².
Do NOT prescribe with baseline severe cytopenia.
Do NOT forget PJP prophylaxis ≥6 months after last anti-CD20 dose.
Do NOT ignore signs of transformation to DLBCL — biopsy on rapid progression, LDH↑.

Monitoring schedule

Monitoring schedule by treatment phase

Standard plan · MON-RITUXIMAB-MONO

Phase	Window	Tests	Checkpoints
baseline	Within 2 weeks before first dose	TEST-CBC, TEST-LFT, TEST-LDH, TEST-CD20-IHC, TEST-HBV-SEROLOGY, TEST-HCV-ANTIBODY, TEST-FLOW-CYTOMETRY	Confirm CD20+ histology HBV status + entecavir prophylaxis if HBsAg+ or anti-HBc+
induction	Day 1 of each weekly induction × 4	TEST-CBC, TEST-LFT	Infusion reactions especially first dose
maintenance	Every 2 months × 2 years	TEST-CBC, TEST-LFT, TEST-LDH	HBV-DNA quarterly during therapy and 12 mo post Disease assessment clinically; imaging if concern
follow_up	Every 6 months × 5 years post-treatment	TEST-CBC, TEST-LFT, TEST-LDH	Surveillance for relapse + transformation

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Baseline

Within 2 weeks before first dose

Induction · R-Bendamustine for relapsed marginal zone lymphoma (post-rituximab failure)

28-day cycles × 6 cycles

Maintenance

Every 2 months × 2 years

Follow-up

Every 6 months × 5 years post-treatment

MDT brief

Discussion questions (3, 2 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
BLOCKING OQ-BIOMARKER-CD20-IHC
What is the status of CD20 expression by immunohistochemistry (BIO-CD20-IHC)? It is required by track(s): IND-SMZL-2L-BR. Expected value: positive (CD20+).
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.
→ pathologist

MDT talk tree (4 steps)

#	Owner	Topic	Action
1	pathologist	Biomarker status BLOCKING	What is the status of CD20 expression by immunohistochemistry (BIO-CD20-IHC)? It is required by track(s): IND-SMZL-2L-BR. Expected value: positive (CD20+).
2	pathologist	Pathology confirmation BLOCKING	Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated.
3	radiologist	Staging / disease burden	Has complete staging been done (Lugano + PET/CT or CT)?
4	hematologist	Specialist review	Lymphoma diagnosis — leading specialty for treatment management.

Skills (required) — mandatory virtual specialists (1)

Hematologist / oncohematologist required
Lymphoma diagnosis — leading specialty for treatment management.

Skills (recommended) — for consideration (1)

Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-CD20-CONFIRMATION, OQ-BIOMARKER-CD20-IHC

Data quality

Incomplete for default-track review. Default-track review is incomplete until required biomarker gaps are resolved.

Biomarker coverage: 0/1 known (0%), 1 missing, 1 default-track gaps
Missing critical: cd20_ihc_status, lugano_stage
Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
Unevaluated RedFlags: RF-SMZL-FRAILTY-AGE, RF-SMZL-HIGH-RISK-BIOLOGY, RF-SMZL-INFECTION-SCREENING, RF-SMZL-ORGAN-DYSFUNCTION, RF-SMZL-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-CD20-IHC`	CD20 expression by immunohistochemistry	pathologist	yes	IND-SMZL-2L-BR	Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive (CD20+)

Technical MDT skill metadata (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-BSH-MZL-2024: British Society for Haematology — Marginal Zone Lymphoma Guideline (2024)
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)

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: 2026-05-13.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT01137825	Registry of Older Patients With Cancer	N/A	RECRUITING	UNC Lineberger Comprehensive Cancer Center	—	Single country
NCT04223765	Study of Kappa Chimeric Antigen Receptor (CAR) T Lymphocytes Co-Expressing the Kappa and CD28 CARs for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.	PHASE1	RECRUITING	UNC Lineberger Comprehensive Cancer Center	—	Phase 1 only Small N (<50) Single country
NCT06712459	Integrated Molecular and Clinical Profiling of Transformed Splenic Marginal Zone Lymphoma	N/A	RECRUITING	International Extranodal Lymphoma Study Group (IELSG)	—	—
NCT06796998	Epcoritamab in Patients With Newly Diagnosed Marginal Zone Lymphoma (MZL)	PHASE2	RECRUITING	Izidore Lossos, MD	—	Small N (<50) Single country
NCT01137643	Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer	N/A	RECRUITING	UNC Lineberger Comprehensive Cancer Center	—	Surrogate endpoint only Single country
NCT00935090	3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer	N/A	RECRUITING	Barbara Ann Karmanos Cancer Institute	—	Single country
NCT06859008	Zanubrutinib in Combination With Sonrotoclax for the Treatment of Underrepresented Ethnic and Racial Minorities With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma	PHASE1	RECRUITING	City of Hope Medical Center	—	Phase 1 only Small N (<50) Single country
NCT00923507	Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)	N/A	RECRUITING	National Heart, Lung, and Blood Institute (NHLBI)	—	Single country
NCT06544265	SynKIR-310 for Relapsed/Refractory B-NHL	PHASE1	RECRUITING	Verismo Therapeutics	—	Phase 1 only Small N (<50) Single country
NCT05544019	Study of SGR-1505 in Mature B-Cell Neoplasms	PHASE1	RECRUITING	Schrödinger, Inc.	UA	Phase 1 only

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 R-Bendamustine for relapsed marginal zone lymphoma (post-rituximab failure) (REG-R-BENDAMUSTINE-RELAPSED-MZL)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Trial · NCT01137825 Registry of Older Patients With Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04223765 Study of Kappa Chimeric Antigen Receptor (CAR) T Lymphocytes Co-Expressing the Kappa and CD28 CARs for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06712459 Integrated Molecular and Clinical Profiling of Transformed Splenic Marginal Zone Lymphoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06796998 Epcoritamab in Patients With Newly Diagnosed Marginal Zone Lymphoma (MZL) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT01137643 Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT00935090 3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06859008 Zanubrutinib in Combination With Sonrotoclax for the Treatment of Underrepresented Ethnic and Racial Minorities With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT00923507 Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06544265 SynKIR-310 for Relapsed/Refractory B-NHL No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05544019 Study of SGR-1505 in Mature B-Cell Neoplasms UA site available — verify enrollment status with site	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-13.

plan_id: PLAN-VAR-SPLENIC-MZL-RELAPSED-V1 | version: 1 | generated: 2026-05-13T10:01:52.703490+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.