Patient
DLBCL-2L-POLABR-002 · Algorithm: ALGO-DLBCL-2L
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-CD79B-IHC | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
Primary current-line option
- Indication
- IND-DLBCL-2L-POLA-R-BENDAMUSTINE
- Regimen
- Polatuzumab vedotin + Rituximab + Bendamustine (Pola-BR), 6 cycles
- Drugs + NSZU
- Polatuzumab vedotin (DRUG-POLATUZUMAB-VEDOTIN) 1.8 mg/kg · IV day 2 of cycle 1, day 1 of cycles 2-6 · IV ✗ Not registered in UA
- Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 of each 21-day cycle · IV ✓ NSZU covered
- Bendamustine (DRUG-BENDAMUSTINE) 90 mg/m² · IV days 2-3 of each 21-day cycle · IV ⚠ NSZU — not for this indication
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS, SUP-GCSF-NEUTROPENIA
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS, CI-BORTEZOMIB-SEVERE-NEUROPATHY, CI-SEVERE-CYTOPENIA-BR
- Reason
- Primary current-line option selected by ALGO-DLBCL-2L at step 3.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-DLBCL-2L-LISOCEL
- Regimen
- Lisocabtagene maraleucel (liso-cel) CAR-T 2L for primary-refractory or early-relapse LBCL (TRANSFORM)
- Drugs + NSZU
Before main therapy: lymphodepletion — lymphocyte depletion before CAR-T to enable cell engraftment (Flu/Cy days -5 to -3 per TRANSFORM protocol)
- Fludarabine (DRUG-FLUDARABINE) 30 mg/m² IV daily × 3 days (lymphodepleting conditioning) · Days -5 to -3 before liso-cel infusion · IV ⚠ NSZU — not for this indication
- Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 300 mg/m² IV daily × 3 days (lymphodepleting conditioning) · Days -5 to -3 before liso-cel infusion · IV ⚠ NSZU — not for this indication
- Lisocabtagene maraleucel (DRUG-LISOCABTAGENE-MARALEUCEL) Target 100 × 10⁶ CAR+ viable T cells (50 × 10⁶ CD8+ component + 50 × 10⁶ CD4+ component, separately manufactured then administered sequentially) · Single IV infusion day 0, 2-7 days after lymphodepletion completion; CD8 component infused first, followed by CD4 component · IV ✗ Not registered in UA
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS, SUP-IVIG-HYPOGAMMA
- Hard contraindications
- CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB, 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-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-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 | — | 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 | — | all tracks |
| TEST-B2-MICROGLOBULIN | Beta-2 Microglobulin | Standard | lab | — | standard |
| TEST-ECHO | Echocardiography | Standard | imaging | — | aggressive |
| TEST-IMMUNOGLOBULINS | Quantitative Immunoglobulins | Standard | lab | — | aggressive |
| TEST-LN-CORE-BIOPSY | Core LN Biopsy | Standard | histology | — | all tracks |
| TEST-MRI-BRAIN-CONTRAST | MRI brain with contrast | Standard | imaging | — | aggressive |
| 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
- Composite eligibility for autologous stem-cell transplantation (ASCT) consolidation: ECOG ≤2 AND adequate cardiac function (LVEF ≥50%, no NYHA III-IV) AND adequate pulmonary function (DLCO ≥50% or absent severe COPD/fibrosis) AND adequate hepatic function (bilirubin ≤2× ULN, AST/ALT ≤3× ULN) AND adequate renal function (CrCl ≥30 mL/min) AND age <70 (lymphoma/MM standard) or <65 (AML standard) AND no active uncontrolled infection AND no second active malignancy. Used to gate ASCT consolidation in MM 1L (CASSIOPEIA, GRIFFIN), DLBCL/PTCL salvage (CORAL, ECHELON-2 follow-up), Hodgkin salvage (post-second-line PR/CR), AML CR1 in non-favorable risk if alloHCT donor unavailable.
RF-ASCT-ELIGIBLE-COMPOSITE
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
- 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-DLBCL-2L-POLA-R-BENDAMUSTINE)
- Do NOT prescribe with baseline Grade ≥2 peripheral neuropathy — MMAE toxicity will progress to permanent disability.
- Do NOT start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ — anti-CD20 reactivation.
- Do NOT prescribe when CrCl <30 — bendamustine renal-cleared metabolites are dangerous; consider Pola-R without bendamustine.
- Do NOT skip GCSF prophylaxis — combined myelosuppression of bendamustine + polatuzumab.
- Do NOT prescribe with concomitant strong CYP3A4 inhibitor without monitoring — increased MMAE toxicity.
- Do NOT confirm the plan without a verified funding pathway for polatuzumab.
- Do NOT use in transplant-eligible patients as 2L — first salvage R-DHAP/R-ICE → autoSCT.
Aggressive plan (IND-DLBCL-2L-LISOCEL)
- Do NOT prescribe prophylactic systemic corticosteroids — suppresses CAR-T expansion + reduces efficacy.
- Do NOT initiate without on-site tocilizumab (minimum 2 doses) BEFORE infusion — fatal CRS possible.
- Do NOT do this at a center without CAR-T accreditation (FACT/JACIE/REMS) — toxicity management requires a specialized team + ICU access.
- НЕ пропускати baseline brain MRI — pre-existing CNS disease (CNS-2/3) була exclusion в TRANSFORM; ризик fatal ICANS значно вищий.
- Do NOT ignore interim bridging chemotherapy (3-4 week manufacturing window) — disease progression in this window reduces efficacy.
- Do NOT prescribe in active uncontrolled infection — lymphodepletion + CRS = high mortality.
- Do NOT forget IVIG for long-term hypogammaglobulinemia (IgG <400 + recurrent infections) — B-cell aplasia can persist >12 months.
- НЕ застосовувати у транспланта-непридатних пацієнтів за цим показанням — TRANSFORM enrolment вимагав transplant-intent; для transplant-ineligible 2L див. PILOT cohort (окрема Indication, future).
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Polatuzumab vedotin + Rituximab + Bendamustine (Pola-BR), 6 cycles
21-day cycles × 6
MDT brief
Discussion questions (2, 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
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 | radiologist | Staging / disease burden | Has complete staging been done (Lugano + PET/CT or CT)? |
| 3 | hematologist | Specialist review | Lymphoma diagnosis — leading specialty for treatment management. |
| 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: 2/2 known (100%), 0 missing, 0 default-track gaps
- Missing critical: cd20_ihc_status, lugano_stage
- Missing recommended: fib4_index, pet_ct_date
- Unevaluated RedFlags: RF-AAIPI-HIGH, RF-DLBCL-CART-INELIGIBLE-POST-2L, RF-DLBCL-CD20-POS-EPCORITAMAB-CANDIDATE, RF-DLBCL-CD20-POS-GLOFITAMAB-CANDIDATE, RF-DLBCL-CD79B-MUT-MCD-CANDIDATE, RF-DLBCL-CNS-RISK, RF-DLBCL-FRAILTY-AGE, RF-DLBCL-HIGH-RISK-BIOLOGY, RF-DLBCL-INFECTION-SCREENING, RF-DLBCL-ORGAN-DYSFUNCTION, RF-DLBCL-TRANSFORMATION-PROGRESSION, RF-IPI-HIGH, RF-IPI-INTERMEDIATE, RF-IPI-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 | 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-TRANSFORM-KAMDAR-2022: Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial (2022)
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 Polatuzumab vedotin + Rituximab + Bendamustine (Pola-BR), 6 cycles (REG-POLA-R-BENDAMUSTINE) 1/3 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Lisocabtagene maraleucel (liso-cel) CAR-T 2L for primary-refractory or early-relapse LBCL (TRANSFORM) (REGIMEN-LISOCEL-DLBCL-2L) 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.