Patient
ALCL-RELAPSED-001 · Algorithm: ALGO-ALCL-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 |
|---|
| BIO-CD30-IHC | CD30 expression — universal (~100%) in systemic anaplastic large-cell lymphoma (ALK-positive and ALK-negative) | IA | - SRC-NCCN-BCELL-2025
- SRC-ESMO-PTCL-2024
Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap. | CD30 expression is a defining feature of anaplastic large-cell lymphoma (sALCL); brentuximab vedotin (BV) targets CD30 with an auristatin payload. 1L sALCL: BV + CHP (cyclophosphamide / doxorubicin / prednisone, replacing vincristine) is preferred over CHOP per ECHELON-2 (Horwitz Lancet 2019 — mPFS 48 vs 21 mo, HR 0.71; OS HR 0.66) per SRC-NCCN-BCELL-2025, SRC-ESMO-PTCL-2024. R/R sALCL: BV monotherapy was the basis of FDA accelerated approval (Pro JCO 2012 — ORR 86%, CR 57%) and is preferred salvage. Pediatric ALCL: AHOD1331 supports BV + AVEPC. | BV + CHP — 1L sALCL per SRC-NCCN-BCELL-2025, SRC-ESMO-PTCL-2024
BV monotherapy — R/R sALCL salvage per SRC-NCCN-BCELL-2025
consolidative autologous HCT in CR1 (high-risk subgroups per SRC-NCCN-BCELL-2025) | - SRC-NCCN-BCELL-2025
- SRC-ESMO-PTCL-2024
|
Primary current-line option
- Indication
- IND-ALCL-2L-BENDAMUSTINE
- Regimen
- Bendamustine monotherapy 90 mg/m² days 1+2 q21d — r/r PTCL incl ALCL
- Drugs + NSZU
- Bendamustine (DRUG-BENDAMUSTINE) 90 mg/m² IV · Days 1 and 2 of each 21-day cycle, up to 6 cycles or until progression · IV ⚠ NSZU — not for this indication
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-ANTIEMETIC-PREMED
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS, CI-SEVERE-CYTOPENIA-BR
- Reason
- Primary current-line option selected by ALGO-ALCL-2L at step 3.
Other current-line alternatives (3 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-ALCL-2L-BRENTUXIMAB-MONO
- Regimen
- Brentuximab vedotin monotherapy (1.8 mg/kg IV q3 weeks × up to 16 cycles) for r/r systemic ALCL
- Drugs + NSZU
- Brentuximab vedotin (DRUG-BRENTUXIMAB-VEDOTIN) 1.8 mg/kg (max 180 mg) · IV over 30 min every 21 days × up to 16 cycles or progression / toxicity · IV ✓ NSZU covered
- Supportive care
- SUP-PJP-PROPHYLAXIS
- Hard contraindications
- CI-BORTEZOMIB-SEVERE-NEUROPATHY
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-ALCL-2L-CRIZOTINIB-ALKPOS
- Regimen
- Crizotinib 250 mg PO BID continuous — r/r ALK+ ALCL
- Drugs + NSZU
- Crizotinib (DRUG-CRIZOTINIB) 250 mg PO BID · Continuous until progression or unacceptable toxicity · PO ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-ALCL-MAINTENANCE-BV-POST-ASCT
- Regimen
- Brentuximab vedotin maintenance post-ASCT for high-risk systemic ALCL (AETHERA-style, 16 cycles)
- Drugs + NSZU
- Brentuximab vedotin (DRUG-BRENTUXIMAB-VEDOTIN) 1.8 mg/kg (max 180 mg) · IV every 21 days × 16 cycles, starting 30-45 days post-ASCT · IV ✓ NSZU covered
- Supportive care
- SUP-PJP-PROPHYLAXIS
- Hard contraindications
- CI-BORTEZOMIB-SEVERE-NEUROPATHY
- 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 | — | all tracks |
| 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) | aggressive |
| TEST-FLOW-CYTOMETRY | Flow Cytometry | Critical | histology | CSD Lab ✓ (code TBC) | standard |
| 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-RENAL-FUNCTION-EGFR | Renal function with eGFR | Critical | lab | — | standard |
| TEST-ECHO | Echocardiography | Standard | imaging | — | all tracks |
| TEST-LN-CORE-BIOPSY | Core LN Biopsy | Standard | histology | — | all tracks |
| TEST-PET-CT | FDG PET/CT (whole body) | Standard | imaging | — | all tracks |
| TEST-FIB4 | FIB-4 Index (Fibrosis-4) | Calculation | clinical_assessment | — | standard |
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-ALCL-2L-BENDAMUSTINE)
- Do not start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ — alkylator immunosuppression risk.
- Do not prescribe with severe baseline cytopenia (CI-SEVERE-CYTOPENIA-BR).
- Do not use full-dose bendamustine at FIB-4 >3.25 — reduce to 70 mg/m².
- Do not use full dose at CrCl 30-60 — reduce to 70 mg/m².
- Do not forget PJP prophylaxis (cotrimoxazole) — continue ≥6 months after the last dose.
- Do not skip the plan for alloSCT consolidation in fit transplant-eligible responders — natural history without consolidation is poor.
- Do not forget off-label disclosure — drug registered for B-cell lymphomas; ALCL off-label via existing supply route.
- Do not combine with brentuximab without MDT input — combination toxicity (cytopenia + infection) substantial.
Standard plan (IND-ALCL-2L-BRENTUXIMAB-MONO)
- Do not combine with bleomycin — additive lethal pulmonary toxicity (absolute).
- Do not prescribe with pre-existing Grade ≥2 peripheral neuropathy — Grade ≥2 = absolute CI.
- Do not skip baseline CD30 IHC verification — ALCL universally CD30+ but mandatory documentation for funding.
- Do not ignore hepatitis screening + entecavir prophylaxis if HBsAg+ or anti-HBc+.
- Do not forget PJP prophylaxis throughout cycles + ≥6 months after the last dose.
- Do not stop at Grade 1-2 neuropathy — reduce dose to 1.2 mg/kg + continue; permanent discontinuation for Grade ≥3.
- Do not prescribe without funding pathway clarification — brentuximab is NOT NSZU-reimbursed for r/r ALCL.
- Do not skip the plan for alloSCT consolidation in fit transplant-eligible responders — natural history without consolidation is poor.
Aggressive plan (IND-ALCL-2L-CRIZOTINIB-ALKPOS)
- Do not prescribe without verified ALK rearrangement (IHC + FISH) — drug effective only in ALK+ subset (~70% systemic ALCL).
- Do not ignore baseline + serial QTc + visual examinations — visual disturbances (60%), QTc prolongation, bradycardia.
- Do not combine with QT-prolonging drugs without strict monitoring.
- Do not prescribe with concomitant strong CYP3A inhibitor without dose reduction.
- Do not ignore pneumonitis warning — cough/fever/dyspnea = HRCT immediately + permanent discontinuation if confirmed.
- Do not skip the plan for alloSCT consolidation in fit transplant-eligible responders — TKI monotherapy is not curative.
- Do not forget off-label disclosure — drug registered for ALK+ NSCLC; ALCL off-label use requires MDT documentation.
- Do not stop at mild visual disturbances (~60% common, transient) — counseling + dose reduction for persistent.
Standard plan (IND-ALCL-MAINTENANCE-BV-POST-ASCT)
- Do not continue maintenance at Grade ≥2 neuropathy — permanent discontinuation.
- Do not combine with bleomycin — lethal pulmonary toxicity (absolute).
- Do not start earlier than 30 days post-ASCT — engraftment safety.
- Do not skip baseline ECG / LVEF if anthracycline-rich pre-ASCT.
- Do not ignore HBV-prophylaxis if HBsAg+ or anti-HBc+.
- Do not skip PJP prophylaxis throughout maintenance + ≥6 months after.
- Do not substitute for pre-ASCT salvage — poor pre-ASCT response is not corrected by maintenance.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Bendamustine monotherapy 90 mg/m² days 1+2 q21d — r/r PTCL incl ALCL
21-day cycles × Up to 6 (longer if sustained response + tolerability)
Standard plan
Induction · Brentuximab vedotin monotherapy (1.8 mg/kg IV q3 weeks × up to 16 cycles) for r/r systemic ALCL
21-day cycles × Up to 16 (longer if sustained CR + toxicity acceptable)
Aggressive plan
Induction · Crizotinib 250 mg PO BID continuous — r/r ALK+ ALCL
28-day cycles × Continuous
Standard plan
Induction · Brentuximab vedotin maintenance post-ASCT for high-risk systemic ALCL (AETHERA-style, 16 cycles)
21-day cycles × 16 cycles (~12 months) starting 30-45 days post-ASCT
MDT brief
Discussion questions (5, 2 blocking)
BLOCKING OQ-HBV-SEROLOGY
Has HBV serology (HBsAg, anti-HBc total) been done? Status must be known before starting anti-CD20 therapy.
Anti-CD20 without HBV prophylaxis in HBsAg+/anti-HBc+ patients carries significant reactivation risk (CI-HBV-NO-PROPHYLAXIS).
→ infectious_disease_hepatology
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
OQ-BIOMARKER-ALK-REARRANGEMENT
What is the status of ALK rearrangement (most commonly NPM1-ALK t(2;5)) (BIO-ALK-REARRANGEMENT)? It is required by track(s): IND-ALCL-2L-CRIZOTINIB-ALKPOS. Expected value: positive (NPM1-ALK most common; other ALK partners also responsive).
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist
MDT talk tree (6 steps)
| # | Owner | Topic | Action |
|---|
| 1 | infectious_disease_hepatology | Infection / hepatic safety BLOCKING | Has HBV serology (HBsAg, anti-HBc total) been done? Status must be known before starting anti-CD20 therapy. |
| 2 | pathologist | Pathology confirmation BLOCKING | Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated. |
| 3 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 4 | molecular_geneticist | Biomarker status | What is the status of ALK rearrangement (most commonly NPM1-ALK t(2;5)) (BIO-ALK-REARRANGEMENT)? It is required by track(s): IND-ALCL-2L-CRIZOTINIB-ALKPOS. Expected value: positive (NPM1-ALK most common; other ALK partners also responsive). |
| 5 | radiologist | Staging / disease burden | Has complete staging been done (Lugano + PET/CT or CT)? |
| 6 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
Skills (required) — mandatory virtual specialists (1)
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.
Owns: OQ-BIOMARKER-ALK-REARRANGEMENT
- 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: 1/2 known (50%), 1 missing, 0 default-track gaps
- Missing critical: cd20_ihc_status, hbsag blocks: RF-ALCL-INFECTION-SCREENING, anti_hbc_total blocks: RF-ALCL-INFECTION-SCREENING, lugano_stage
- Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
- Unevaluated RedFlags: RF-ALCL-FRAILTY-AGE, RF-ALCL-INFECTION-SCREENING, RF-ALCL-ORGAN-DYSFUNCTION, RF-ALCL-TRANSFORMATION-PROGRESSION
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 | HBsAg hbsag
| infectious_disease_hepatology | Identifies active HBV infection and prophylaxis need before anti-CD20 or other immunosuppressive therapy. | Order or document HBsAg before treatment start. | RF-ALCL-INFECTION-SCREENING |
| CRITICAL | Total anti-HBc anti_hbc_total
| infectious_disease_hepatology | Detects prior HBV exposure and reactivation risk. | Order or document total anti-HBc and decide prophylaxis/monitoring. | RF-ALCL-INFECTION-SCREENING |
| 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. | - |
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-ALK-REARRANGEMENT | ALK rearrangement (most commonly NPM1-ALK t(2;5)) | molecular_geneticist | no | IND-ALCL-2L-CRIZOTINIB-ALKPOS | Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive (NPM1-ALK most common; other ALK partners also responsive) |
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-ECHELON-2-HORWITZ-2019: Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial (2019)
- 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: 2026-06-11 · 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 Bendamustine monotherapy 90 mg/m² days 1+2 q21d — r/r PTCL incl ALCL (REG-BENDAMUSTINE-PTCL) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Brentuximab vedotin monotherapy (1.8 mg/kg IV q3 weeks × up to 16 cycles) for r/r systemic ALCL (REG-BV-MONO-SYSTEMIC-ALCL) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Crizotinib 250 mg PO BID continuous — r/r ALK+ ALCL (REG-CRIZOTINIB-ALCL) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Brentuximab vedotin maintenance post-ASCT for high-risk systemic ALCL (AETHERA-style, 16 cycles) (REG-BRENTUXIMAB-MAINTENANCE-ALCL) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-06-11.