Patient
MCL-3L-PIRTO-001 · Algorithm: ALGO-MCL-3L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| No clinically actionable variants matched in this profile. |
| 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
- 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.
- 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.
RF-CAR-T-ELIGIBLE
- 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.
RF-PRIOR-BTKI-PROGRESSION
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_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 · 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)
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: 2026-05-12 · 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 |
|---|
| 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: 2026-05-12.