Treatment plan — Mantle Cell Lymphoma

OpenOnco · MCL · 3L+ · Pirtobrutinib post-covalent-BTKi (BRUIN MCL-321)

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OpenOnco · Treatment Plan

Treatment plan — Mantle Cell Lymphoma

PLAN-MCL-3L-PIRTO-001-V1 · v1 · 2026-08-18

Patient

MCL-3L-PIRTO-001 · Algorithm: ALGO-MCL-3L

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
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
BIO-CYCLIN-D1-IHC	Not in KB — ask clinician to verify

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-MCL-3L-PIRTOBRUTINIB

Regimen

Pirtobrutinib monotherapy continuous (BRUIN MCL schedule, post-cBTKi)

Drugs + NSZU

Pirtobrutinib (DRUG-PIRTOBRUTINIB) 200 mg PO once daily · Continuous until progression or unacceptable toxicity · PO ✗ Not registered in UA

Reason

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

Other current-line alternatives (1 tracks)

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

Aggressive plan

Indication

IND-MCL-3L-BREXUCEL-CART

Regimen

Brexucabtagene autoleucel (brexu-cel) CAR-T for r/r MCL — single infusion after lymphodepletion (ZUMA-2)

Drugs + NSZU

Before main therapy: lymphodepletion — lymphocyte depletion before CAR-T to enable cell engraftment

Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 500 mg/m²/day · IV days -5, -4, -3 · IV ⚠ NSZU — not for this indication
Fludarabine (DRUG-FLUDARABINE) 30 mg/m²/day · IV days -5, -4, -3 · IV ⚠ NSZU — not for this indication

Brexucabtagene autoleucel (DRUG-BREXUCABTAGENE-AUTOLEUCEL) Target 2 × 10^6 anti-CD19 CAR+ T-cells/kg (max 2 × 10^8 total) · Single IV infusion day 0, after lymphodepletion completed · IV ✗ Not registered in UA

Supportive care

SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-IVIG-HYPOGAMMA, SUP-TLS-PROPHYLAXIS

Hard contraindications

CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB

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-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)	standard
TEST-FLOW-CYTOMETRY	Flow Cytometry	Critical	histology	CSD Lab ✓ (code TBC)	aggressive
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-PREGNANCY	Beta-HCG	Critical	lab	—	aggressive
TEST-B2-MICROGLOBULIN	Beta-2 Microglobulin	Standard	lab	—	standard
TEST-ECHO	Echocardiography	Standard	imaging	—	all tracks
TEST-IMMUNOGLOBULINS	Quantitative Immunoglobulins	Standard	lab	—	all tracks
TEST-LN-CORE-BIOPSY	Core LN Biopsy	Standard	histology	—	aggressive
TEST-MRI-BRAIN-CONTRAST	MRI brain with contrast	Standard	imaging	—	desired (aggressive)
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

Composite eligibility for CAR-T cell therapy: ECOG ≤2 AND adequate organ function (LVEF ≥40%, CrCl ≥30 mL/min, bilirubin ≤2× ULN, AST/ALT ≤5× ULN, no severe pulmonary disease) AND no active uncontrolled CNS disease AND adequate bridging plan available AND no active uncontrolled infection. Used to gate referral to axi-cel, brexu-cel, liso-cel, tisa-cel, ide-cel, cilta-cel.
Composite gate harmonized across landmark CAR-T trials (ZUMA-1, TRANSCEND, JULIET, ZUMA-7, TRANSFORM, ZUMA-2, KarMMa, CARTITUDE-1). Real-world expansion of criteria (CIBMTR analysis): ECOG 2 acceptable with consultant judgment; LVEF…
RF-CAR-T-ELIGIBLESRC-ZUMA-1-NEELAPU-2017SRC-ZUMA-7-LOCKE-2022
Progression on covalent BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib). Triggers selection of non-covalent BTKi (pirtobrutinib), BCL2i (venetoclax-based regimens), CAR-T (lisocabtagene maraleucel, brexucabtagene autoleucel), or PI3Ki — depending on disease (CLL, MCL, WM). Resistance often driven by BTK C481S or PLCG2 mutation.
CLL: BRUIN study (Mato 2023) — pirtobrutinib ORR 82% in BTKi-pretreated; venetoclax + obinutuzumab also active (CLL14 was 1L but venetoclax monotherapy MURANO post-BTKi shows efficacy); CAR-T (liso-cel) per TRANSCEND-CLL-004. MCL: BRUIN…
RF-PRIOR-BTKI-PROGRESSIONSRC-NCCN-BCELL-2025SRC-ESMO-CLL-2024

CONTRA-AGGRESSIVE

Hard contraindications to escalation

Alemtuzumab causes profound, prolonged CD4+ T-cell depletion (median recovery 9-12 months). Active uncontrolled infection at baseline becomes life-threatening once cellular immunity collapses. HIV-positive status is itself an absolute contraindication — alemtuzumab on top of HIV immunosuppression has unacceptable infectious mortality. CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB

What NOT to do

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

Standard plan (IND-MCL-3L-PIRTOBRUTINIB)

Do not prescribe without verified prior cBTKi exposure — Cat 2A indication restricts use to post-cBTKi setting.
Do not stop on transient AE without reassessment — for post-cBTKi MCL alternatives are few.
Do not skip baseline ECG + cardiology assessment — afib reduced but possible.
Do not combine with anticoagulants without strict monitoring — bleeding risk persists.
Do not prescribe with concomitant strong CYP3A4 inhibitor without dose reduction to 100 mg PO QD.
Do not confirm plan without funding pathway — drug not registered in Ukraine.
Do not forget progression monitoring — for TP53-mut or blastoid MCL, early CAR-T-referral planning is recommended, even during pirtobrutinib bridge.

Aggressive plan (IND-MCL-3L-BREXUCEL-CART)

Do not prescribe prophylactic systemic corticosteroids — suppresses CAR-T expansion + reduces efficacy.
Do not start without on-site tocilizumab (minimum 2 doses) BEFORE infusion — fatal CRS possible.
Do not perform at a center without CAR-T accreditation (FACT/JACIE/REMS) — toxicity management requires a specialized team + ICU access.
Do not skip baseline brain MRI — pre-existing CNS disease risk of fatal ICANS significantly higher (higher in MCL than DLBCL).
Do not ignore bridging therapy — TP53-mut or blastoid MCL progresses fast in the 3-4 wk manufacturing window.
Do not prescribe with active uncontrolled infection — lymphodepletion + CRS = high mortality.
Do not use axi-cel instead of brexu-cel — leukemic-phase MCL apheresis contamination problematic without CD19-depletion process step.
Do not forget IVIG for long-term hypogammaglobulinemia (IgG <400 + recurrent infections).

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 (venetoclax)	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 · Pirtobrutinib monotherapy continuous (BRUIN MCL schedule, post-cBTKi)

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

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 (4 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.

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

Data quality

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

Biomarker coverage: 1/1 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 (3/16 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)
SRC-ZUMA-2-WANG-2020: KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma (2020)

Experimental options (clinical trials)

Last synced: 2026-08-18 · 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 Pirtobrutinib monotherapy continuous (BRUIN MCL schedule, post-cBTKi) (REG-PIRTOBRUTINIB-MCL) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Aggressive plan Brexucabtagene autoleucel (brexu-cel) CAR-T for r/r MCL — single infusion after lymphodepletion (ZUMA-2) (REG-CAR-T-BREXUCEL-MCL) 1/3 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-18.

plan_id: PLAN-MCL-3L-PIRTO-001-V1 | version: 1 | generated: 2026-08-18T07:59:48.897311+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.