Treatment plan — Mantle Cell Lymphoma

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OpenOnco · Treatment Plan

Treatment plan — Mantle Cell Lymphoma

PLAN-VAR-MCL-BIOMARK-V1 · v1 · 2026-05-13

Patient

VAR-MCL-BIOMARK · Algorithm: ALGO-MCL-1L

DiagnosisMantle Cell Lymphoma

MOH / ICD-10C83.1

ICD-O-39673/3

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
BIO-CCND1-IHC	cyclin D1 IHC (universal in MCL; defines diagnosis with t(11;14) FISH)	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response)	Cyclin D1 IHC is a defining diagnostic marker of MCL (positive in >95%; SOX11 used in cyclin D1-negative variant). Drives DIS-MCL diagnosis but does not 'select' therapy independently of t(11;14).	per DIS-MCL algorithm (BTKi-centric)	SRC-NCCN-BCELL-2025 SRC-ESMO-MCL-2024
BIO-T11-14-IGH-CCND1	t(11;14)(q13;q32) IGH/CCND1	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response)	t(11;14) IGH/CCND1 is the defining genetic lesion of MCL — drives cyclin D1 overexpression. BTKi (acalabrutinib + rituximab — TRIANGLE, Dreyling Lancet 2024; ECHO — Wang NEJM 2024) is the new 1L standard regardless of fitness for TP53-mut; high-dose AraC + autoSCT historically (LyMa, MCL Younger). Venetoclax (CCND1 → BCL2-mediated anti-apoptosis rationale) active R/R.	acalabrutinib + bendamustine + rituximab (1L) BR or R-CHOP/R-DHAP + autoSCT (1L fit, TP53-WT) venetoclax + ibrutinib (R/R) brexu-cel (R/R 2L+)	SRC-NCCN-BCELL-2025 SRC-ESMO-MCL-2024

⚠️ Not included in plan

Biomarker	Status
BIO-CD20-IHC	BIO definition in KB; no ESCAT BMA entry — verify with clinician
BIO-CD5-IHC	BIO definition in KB; no ESCAT BMA entry — verify with clinician
BIO-MCL-MIPI	BIO definition in KB; no ESCAT BMA entry — verify with clinician

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-MCL-1L-BTKI-R

Regimen

Acalabrutinib + Rituximab (continuous BTKi + R)

Drugs + NSZU

Acalabrutinib (DRUG-ACALABRUTINIB) 100 mg PO BID continuous · PO twice daily until progression or intolerance · PO ⚠ NSZU — not for this indication
Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV weekly × 4 (induction), then every 8 weeks × 2 years · IV ✓ NSZU covered

Hard contraindications

CI-HBV-NO-PROPHYLAXIS

Reason

Primary current-line option selected by ALGO-MCL-1L at step 3.

Other current-line alternatives (1 tracks)

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

Aggressive plan

Indication

IND-MCL-1L-INTENSIVE

Regimen

Intensive 1L MCL: alternating R-CHOP / R-DHAP × 6 cycles + autoSCT consolidation + R maintenance

Drugs + NSZU

Induction — induction: 6 alternating cycles R-CHOP and R-DHAP (3 + 3); anti-CD20 with anthracycline-containing and HiDAC-containing blocks for maximum remission before autoSCT

Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 each cycle (R-CHOP + R-DHAP) · IV ✓ NSZU covered
Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 750 mg/m² · IV day 1 of R-CHOP cycles only · IV ⚠ NSZU — not for this indication
Doxorubicin (DRUG-DOXORUBICIN) 50 mg/m² · IV day 1 of R-CHOP cycles only · IV ✓ NSZU covered
Vincristine (DRUG-VINCRISTINE) 1.4 mg/m² (cap 2 mg) · IV day 1 of R-CHOP cycles only · IV ⚠ NSZU — not for this indication
Prednisone (DRUG-PREDNISONE) 100 mg · PO days 1-5 of R-CHOP cycles · PO ⚠ NSZU — not for this indication
Dexamethasone (DRUG-DEXAMETHASONE) 40 mg · IV days 1-4 of R-DHAP cycles only · IV ⚠ NSZU — not for this indication
Cytarabine (DRUG-CYTARABINE) 2 g/m² q12h · IV day 2 of R-DHAP cycles (HiDAC component) · IV ⚠ 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
TEST-BM-TREPHINE	Bone Marrow Trephine	Critical	histology	—	aggressive
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)	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
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-LN-EXCISIONAL-BIOPSY	Excisional LN Biopsy	Critical	histology	—	aggressive
TEST-PREGNANCY	Beta-HCG	Critical	lab	—	aggressive
TEST-B2-MICROGLOBULIN	Beta-2 Microglobulin	Standard	lab	—	aggressive
TEST-ECHO	Echocardiography	Standard	imaging	—	all tracks
TEST-PET-CT	FDG PET/CT (whole body)	Standard	imaging	—	all tracks
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

Mantle cell lymphoma with MIPI low risk (MIPI <5.7 / 0-3 simplified points) — supports standard intensified induction in fit younger patients (Nordic / R-DHAP-based) without further treatment escalationRF-MIPI-LOW

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

Standard plan (IND-MCL-1L-BTKI-R)

Do not skip TP53 / Ki67 — TP53-mutant requires consideration of CAR-T pathway and alloSCT consultation.
Do not prescribe without HBV screening + prophylaxis in HBsAg+ / anti-HBc+.
Do not combine with warfarin without strict monitoring.
Do not prescribe with concomitant strong CYP3A4 inhibitor — hold inhibitor or dose-modify acalabrutinib.

Aggressive plan (IND-MCL-1L-INTENSIVE)

Do not prescribe in TP53-mutant or blastoid MCL — chemoimmuno-resistant; direct route to BTKi-based (REG-ACALABRUTINIB-RITUXIMAB).
Do not skip baseline LVEF + cytogenetics + TP53 sequencing before start.
Do not use in age >65 OR ECOG >1 — toxicity overwhelms benefit; route to less intensive.
Do not skip HBV screening + entecavir prophylaxis.
Do not administer vincristine intrathecally — FATAL.

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

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 start

Induction · Acalabrutinib + Rituximab (continuous BTKi + R)

28-day cycles × Acalabrutinib continuous; rituximab × 2 years then off

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 cycle 1

Induction · Intensive 1L MCL: alternating R-CHOP / R-DHAP × 6 cycles + autoSCT consolidation + R maintenance

21-day cycles × 6 alternating (3 R-CHOP + 3 R-DHAP), then BEAM/CBV-conditioned autoSCT, then R maintenance every 2 mo × 3 years

Response assessment

After cycles 2-4 (interim PET-CT)

Follow-up

Every 3 months × 2 years post-treatment

MDT brief

Discussion questions (3, 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

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	radiologist	Staging / disease burden	Has complete staging been done (Lugano + PET/CT or CT)?
4	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
5	molecular_geneticist	Specialist review	Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.

Skills (required) — mandatory virtual specialists (1)

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

Skills (recommended) — for consideration (3)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-CD20-CONFIRMATION

Data quality

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

Biomarker coverage: 5/5 known (100%), 0 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-MCL-BLASTOID-OR-TP53, RF-MCL-BLASTOID-VARIANT, RF-MCL-FRAILTY-AGE, RF-MCL-INFECTION-SCREENING, RF-MCL-ORGAN-DYSFUNCTION, RF-MCL-POST-BTKI-C481-ACTIONABLE, RF-MCL-TRANSFORMATION-PROGRESSION, RF-MIPI-HIGH, RF-MIPI-LOW

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.	-

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-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: 2026-05-13 · 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 + Rituximab (continuous BTKi + R) (REG-ACALABRUTINIB-RITUXIMAB)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Intensive 1L MCL: alternating R-CHOP / R-DHAP × 6 cycles + autoSCT consolidation + R maintenance (REG-MCL-INTENSIVE-RDHAP-AUTOSCT)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary

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

plan_id: PLAN-VAR-MCL-BIOMARK-V1 | version: 1 | generated: 2026-05-13T10:01:52.228389+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.