OpenOnco · Treatment Plan

Treatment plan — DIS-PCNSL

PLAN-BMA-MYD88_L265P_PCNSL-V1 · v1 · 2026-05-04

Patient

BMA-MYD88_L265P_PCNSL · Algorithm: ALGO-PCNSL-1L

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-MYD88-L265P	L265P	IIB	SRC-CIVIC: Level B (Supports, Better Outcome) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	MYD88 L265P present in ~70-90% of PCNSL (often co-mutated with CD79B). Ibrutinib monotherapy crosses BBB and shows activity in R/R PCNSL (Grommes et al. Cancer Discov 2017; Soussain Eur J Cancer 2019). Off-label NCCN-supported in R/R disease.	ibrutinib (R/R PCNSL, off-label NCCN-supported) ibrutinib + HD-MTX-based regimens (trial) MTX-based induction → consolidation per usual PCNSL algorithm	SRC-NCCN-CNS-2025

Treatment options (2 tracks)

Standard plan

★ DEFAULT

Indication

IND-PCNSL-1L-MATRIX

Regimen

MATRix (HD-Methotrexate + HD-Cytarabine + Thiotepa + Rituximab), 4 cycles

Drugs + NSZU

Induction — MATRix induction × 4 cycles — HD-MTX + HD-Cytarabine + thiotepa + rituximab for PCNSL; followed by separate autoSCT consolidation regimen (BCNU + thiotepa)

Methotrexate (DRUG-METHOTREXATE) 3.5 g/m² · IV 24h infusion day 1; leucovorin rescue from h+24 · IV ✓ NSZU covered
Cytarabine (DRUG-CYTARABINE) 2 g/m² BID · IV days 2-3 (4 doses total) · IV ⚠ NSZU — not for this indication
Thiotepa (DRUG-THIOTEPA) 30 mg/m² · IV day 4 · IV ✓ NSZU covered
Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV days -5, 0 · IV ✓ NSZU covered

Supportive care

SUP-HBV-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-GCSF-NEUTROPENIA

Hard contraindications

CI-HBV-NO-PROPHYLAXIS, CI-RENAL-FAILURE-FOR-HD-MTX

Reason

Engine default per algorithm ALGO-PCNSL-1L: {'step': 2, 'outcome': False, 'branch': {'result': 'IND-PCNSL-1L-MATRIX'}, 'fired_red_flags': [], 'winner_red_flag': None}

Aggressive plan

Indication

IND-PCNSL-1L-R-MPV

Regimen

R-MPV (Rituximab + HD-Methotrexate + Procarbazine + Vincristine), 5 cycles q14d

Drugs + NSZU

Rituximab (DRUG-RITUXIMAB) 500 mg/m² · IV day 1 · IV ✓ NSZU covered
Methotrexate (DRUG-METHOTREXATE) 3.5 g/m² · IV 2h infusion day 2; leucovorin rescue · IV ✓ NSZU covered
Vincristine (DRUG-VINCRISTINE) 1.4 mg/m² (max 2 mg) · IV day 2 · IV ⚠ NSZU — not for this indication
Procarbazine (DRUG-PROCARBAZINE) 100 mg/m² · PO days 1-7 odd cycles only · PO ✗ Not registered in UA

Supportive care

SUP-HBV-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS

Hard contraindications

CI-HBV-NO-PROPHYLAXIS, CI-RENAL-FAILURE-FOR-HD-MTX

Reason

Alternative track 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-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	—	standard
TEST-CSF-CYTOLOGY-FLOW	CSF cytology + flow cytometry	Standard	pathology	CSD Lab ✓ (code TBC)	all tracks
TEST-ECHO	Echocardiography	Standard	imaging	—	all tracks
TEST-MRI-BRAIN-CONTRAST	MRI brain with contrast	Standard	imaging	—	all tracks
TEST-SLIT-LAMP-EYE-EXAM	Slit-lamp + dilated fundoscopic exam	Standard	imaging	—	all tracks
TEST-NGS-LYMPHOID-PANEL	Lymphoid NGS Panel	Desired	genomic	CSD Lab ✓ (code TBC)	desired (standard)

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

Age >70 OR ECOG ≥3 OR CrCl 50-70 mL/min — full-dose HD-MTX (≥3.5 g/m²) carries excessive toxicity; reduced-dose MTX (1-3 g/m²) ± rituximab considered.RF-PCNSL-FRAILTY-AGE
Renal dysfunction (CrCl <50 mL/min) — high-dose methotrexate (HD-MTX, ≥3 g/m²) backbone of all PCNSL 1L regimens contraindicated; transition to non-MTX regimen or refer to specialized center.RF-PCNSL-ORGAN-DYSFUNCTION

CONTRA-AGGRESSIVE

Hard contraindications to escalation

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
High-dose methotrexate (≥1 g/m²) is renally cleared and depends on vigorous hydration + alkalinization for safe elimination. CrCl <50 mL/min causes catastrophic MTX accumulation, AKI worsening, mucositis, and myelotoxicity that can be fatal even with leucovorin and glucarpidase rescue. CI-RENAL-FAILURE-FOR-HD-MTX

What NOT to do

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

Standard plan (IND-PCNSL-1L-MATRIX)

Do not give steroids BEFORE diagnostic biopsy — they may destroy lymphoma morphology (false negative).
Do not start HD-MTX without CrCl >50, normal hydration, leucovorin rescue, urine pH >7 — fatal AKI risk.
Do not skip ophthalmology consult — ocular involvement ~20% may be silent.
Do not give IT chemo routinely — CSF involvement is rare (~15%); IT only if CSF cytology+/positive flow.
Do not administer vincristine (if in any supplementary regimen) intrathecally — fatal.

Aggressive plan (IND-PCNSL-1L-R-MPV)

Do not give steroids BEFORE biopsy.
Do not give HD-MTX without monitoring CrCl + MTX levels.
Do not administer vincristine intrathecally.
Do not use full-dose WBRT (45 Gy) in >60 — severe neurocognitive decline.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · MATRix (HD-Methotrexate + HD-C

21-day cycles × 4 cycles induction; followed by autoSCT consolidation (BCNU + thiotepa)

Aggressive plan

Induction · R-MPV (Rituximab + HD-Methotre

14-day cycles × 5-7 cycles induction; followed by HD-cytarabine consolidation OR reduced-dose WBRT 23.4 Gy для CR

MDT brief

Skills (required) — mandatory virtual specialists (1)

Hematologist / oncohematologist required
Lymphoma diagnosis — leading specialty for treatment management.
Owns: OQ-LDH-CURRENT
skill: hematologistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Skills (recommended) — for consideration (2)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-CD20-CONFIRMATION
skill: pathologistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open 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

Data quality

Missing critical: cd20_ihc_status, lugano_stage
Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
Unevaluated RedFlags: RF-PCNSL-HIGH-RISK-BIOLOGY, RF-PCNSL-INFECTION-SCREENING, RF-PCNSL-INTRACRANIAL-PRESSURE, RF-PCNSL-ORGAN-DYSFUNCTION, RF-PCNSL-TRANSFORMATION-PROGRESSION

Skill catalog (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	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)
SRC-NCCN-CNS-2025: NCCN Central Nervous System Cancers (v.3.2025)

Experimental options (clinical trials)

Last synced: 2026-05-04 · 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 MATRix (HD-Methotrexate + HD-Cytarabine + Thiotepa + Rituximab), 4 cycles (REG-MATRIX)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan R-MPV (Rituximab + HD-Methotrexate + Procarbazine + Vincristine), 5 cycles q14d (REG-R-MPV) 1/4 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: 2026-05-04.

plan_id: PLAN-BMA-MYD88_L265P_PCNSL-V1 | version: 1 | generated: 2026-05-04T14:13:16.642595+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.