Patient
DLBCL-LONCAST-001 · Algorithm: ALGO-DLBCL-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 |
Primary current-line option
- Indication
- IND-DLBCL-3L-LONCASTUXIMAB
- Regimen
- Loncastuximab tesirine monotherapy (R/R DLBCL, 3L+; LOTIS-2)
- Drugs + NSZU
- Loncastuximab tesirine (DRUG-LONCASTUXIMAB-TESIRINE) 150 µg/kg IV cycles 1-2; then 75 µg/kg IV from cycle 3 onward · Day 1 every 21 days, until disease progression or unacceptable toxicity · IV ✗ Not registered in UA
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Reason
- Primary current-line option selected by ALGO-DLBCL-3L at step 2; branch-driving red flag: RF-DLBCL-CART-INELIGIBLE-POST-2L.
Other current-line alternatives (3 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-DLBCL-3L-AXICEL-CART
- Regimen
- Axicabtagene ciloleucel (axi-cel) CAR-T — single infusion after lymphodepletion
- 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
- Axicabtagene ciloleucel (DRUG-AXICABTAGENE-CILOLEUCEL) 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
- Hard contraindications
- CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-DLBCL-3L-EPCORITAMAB
- Regimen
- Epcoritamab SC monotherapy for r/r DLBCL ≥3L (EPCORE NHL-1)
- Drugs + NSZU
- Epcoritamab (DRUG-EPCORITAMAB) Cycle 1 step-up: 0.16 mg SC day 1 → 0.8 mg SC day 8 → 48 mg SC day 15 + day 22; then 48 mg SC weekly cycles 1-3, every 2 weeks cycles 4-9, every 4 weeks cycles 10+ until progression or unacceptable toxicity · 28-day cycles; SC injection (abdomen / thigh); first 48 mg dose (cycle 1 day 15) requires 24h hospital monitoring for CRS · SC ✗ Not registered in UA
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB, CI-HBV-NO-PROPHYLAXIS
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-DLBCL-3L-GLOFITAMAB
- Regimen
- Glofitamab IV monotherapy with obinutuzumab pretreatment, fixed-duration 12 cycles, for r/r DLBCL ≥3L (NP30179)
- Drugs + NSZU
- Obinutuzumab (DRUG-OBINUTUZUMAB) 1000 mg IV single dose (Gpt — pretreatment dose; not weight-adjusted at this dose) · Day -7 (7 days before glofitamab cycle 1 day 1); standard anti-CD20 infusion premedication required · IV ⚠ NSZU — not for this indication
- Glofitamab (DRUG-GLOFITAMAB) Cycle 1: 2.5 mg IV day 1 (step-up dose 1) → 10 mg IV day 8 (step-up dose 2) → 30 mg IV day 15 (first full dose); Cycles 2-12: 30 mg IV day 1 of each 21-day cycle; STOP at end of cycle 12 (no maintenance) · 21-day cycles; cycle 1 day 15 first 30 mg dose requires hospital-monitored 4-8h observation for CRS · IV ✗ Not registered in UA
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB, CI-HBV-NO-PROPHYLAXIS
- Reason
- Current-line alternative presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 2 → branch IND-DLBCL-3L-LONCASTUXIMAB
- RF-DLBCL-CART-INELIGIBLE-POST-2L ★ winner: Relapsed/refractory DLBCL post ≥2 prior systemic therapies, NOT a candidate for anti-CD19 CAR-T (axi-cel / liso-cel / tisa-cel) due to frailty, organ dysfunction, comorbidity burden, manufacturing-window risk, prior CAR-T failure, or absent funded referral pathway. Routes 3L+ to loncastuximab tesirine (LOTIS-2 Caimi 2021 Lancet Oncol; ORR 48%, CR 24%, mPFS 4.9 mo, mOS 9.5 mo) — off-the-shelf outpatient ADC ideally suited for non-CAR-T-eligible frail patient. Distinct from universal RF-CAR-T-INELIGIBLE-AGE-COMORBID (which gates on age ≥75 + Charlson ≥4) — this flag covers the broader DLBCL-specific ineligibility composite including UA access constraints (no funded international referral pathway).
SRC-NCCN-BCELL-2025SRC-ESMO-DLBCL-2024
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-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 | — | aggressive |
| 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 | — | aggressive |
| 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 |
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
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
- 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
- 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
- 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
- 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
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-DLBCL-3L-LONCASTUXIMAB)
- Do not prescribe in significant cardiac pathology (LVEF <50%) — fluid retention + effusions can worsen CHF.
- Do not ignore baseline + serial liver tests — hepatotoxicity in ~30%, can be severe.
- Do not prescribe in active infection — neutropenia + lymphopenia will increase septic risk.
- Do not combine with other myelosuppressive agents without adjustment.
- Do not forget thromboprophylaxis for patients with venous thromboembolism risk — ADC + lymphoma combine high-risk.
- Do not continue at grade 3 effusions / edema — hold + diuretic; consider permanent discontinuation.
Aggressive plan (IND-DLBCL-3L-AXICEL-CART)
- Do NOT give 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.
- Do NOT skip baseline brain MRI — pre-existing CNS disease (CNS-2/3) was an exclusion in ZUMA-1; risk of fatal ICANS significantly higher.
- Do NOT skip temporary bridging chemotherapy (3-4 week manufacturing window) — disease progression in this window reduces efficacy.
- Do NOT prescribe with active uncontrolled infection — lymphodepletion + CRS = high mortality.
- Do NOT forget IVIG for prolonged hypogammaglobulinemia (IgG <400 + recurrent infections) — B-cell aplasia may last >12 months.
Aggressive plan (IND-DLBCL-3L-EPCORITAMAB)
- НЕ призначати без cycle-1 corticosteroid prophylaxis (preдnoзолон 100 мг ПО/ВВ + ацетамінофен + дифенгідрамін перед кожною step-up дозою) — істотно знижує ризик CRS.
- НЕ пропускати 24-годинне лікарняне спостереження для першої повної дози 48 мг (цикл 1 день 15) — fatal CRS можливе без on-site моnoторингу.
- НЕ розпочинати без on-site tocilizumab (міnoмум 2 дози) — стандартна терапія CRS Grade ≥2.
- НЕ ігнорувати pre-treatment HBV / HCV / HIV скриnoнг — реактивація HBV вимагає entecavir / tenofovir prophylaxis при HBcAb+.
- НЕ призначати при active uncontrolled infection — імунодеплеція + CRS = high mortality.
- НЕ забувати про PJP / HSV профілактику + IVIG (якщо IgG <400 + рецидивno інфекції) — гіпогаммаглобулінемія + B-cell aplasia спостерігаються довготривало.
- НЕ вводити без перевірки CD20 позитивності на найбільш свіжій біопсії — втрата CD20 після попередньої anti-CD20 терапії = absolute exclusion.
Aggressive plan (IND-DLBCL-3L-GLOFITAMAB)
- НЕ розпочинати без обінутузумабу 1000 мг IV у день -7 — преттрітмент попередньо виснажує B-клітини та критично знижує ризик CRS першої дози глофітамабу.
- НЕ пропускати 4-8-годинне лікарняне спостереження для першої повної дози 30 мг (цикл 1 день 15) — fatal CRS можливе без on-site моnoторингу.
- НЕ призначати без cycle-1 dexamethasone 20 мг IV (або еквіваленту) перед кожною step-up дозою (циклу 1 дno 1, 8, 15) — істотно знижує ризик CRS.
- НЕ розпочинати без on-site tocilizumab (міnoмум 2 дози) — стандартна терапія CRS Grade ≥2.
- НЕ ігнорувати pre-treatment HBV / HCV / HIV скриnoнг — реактивація HBV вимагає entecavir / tenofovir prophylaxis при HBcAb+.
- НЕ призначати при active uncontrolled infection — імунодеплеція + CRS = high mortality.
- НЕ забувати про PJP / HSV профілактику + IVIG (якщо IgG <400 + рецидивno інфекції) — гіпогаммаглобулінемія тимчасова, але присутня впродовж терапії.
- НЕ продовжувати після 12 циклів — фіксована тривалість; повторне лікування при прогресії не встановлено.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Loncastuximab tesirine monotherapy (R/R DLBCL, 3L+; LOTIS-2)
21-day cycles × Until progression or unacceptable toxicity (median 3-5 cycles in LOTIS-2; responders may continue ≥1 year)
Aggressive plan
Induction · Epcoritamab SC monotherapy for r/r DLBCL ≥3L (EPCORE NHL-1)
28-day cycles × Continuous until progression or unacceptable toxicity (no fixed duration)
Aggressive plan
Induction · Glofitamab IV monotherapy with obinutuzumab pretreatment, fixed-duration 12 cycles, for r/r DLBCL ≥3L (NP30179)
21-day cycles × 12 cycles fixed duration; no maintenance; re-treatment on progression not established
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: 1/1 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-LOTIS-2-CAIMI-2021: Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial (2021)
- SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)
- SRC-ZUMA-1-NEELAPU-2017: Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma (2017)
- SRC-ZUMA-7-LOCKE-2022: Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma (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 Loncastuximab tesirine monotherapy (R/R DLBCL, 3L+; LOTIS-2) (REG-LONCASTUXIMAB-TESIRINE) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Axicabtagene ciloleucel (axi-cel) CAR-T — single infusion after lymphodepletion (REG-CAR-T-AXICEL) 1/3 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Epcoritamab SC monotherapy for r/r DLBCL ≥3L (EPCORE NHL-1) (REGIMEN-EPCORITAMAB-MONO-DLBCL-3L) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Glofitamab IV monotherapy with obinutuzumab pretreatment, fixed-duration 12 cycles, for r/r DLBCL ≥3L (NP30179) (REGIMEN-GLOFITAMAB-MONO-DLBCL-3L) 1/2 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.