OpenOnco v0.1.2 · 2026-04-30
UA EN
Try it →
OpenOnco · DIS-DLBCL-NOS · BIO-MYD88-L265P (ESCAT IIB)
← Back to galleryFeedback on this case
OpenOnco · Treatment Plan
Treatment plan — DIS-DLBCL-NOS
PLAN-BMA-MYD88_L265P_DLBCL_NOS-V1 · v1 · 2026-05-04
Patient
BMA-MYD88_L265P_DLBCL_NOS · Algorithm: ALGO-DLBCL-1L

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
BIO-MYD88-L265PL265P (often with CD79B mutation — MCD/C5 cluster)IIB
  • SRC-CIVIC: Level B (Supports, Better Outcome)
  • SRC-CIVIC: Level D (Supports, Sensitivity/Response)
MYD88 L265P in DLBCL marks the ABC/MCD molecular subtype (Schmitz et al. NEJM 2018; Wright Cancer Cell 2020). Ibrutinib improves OS specifically in MCD/N1/A53 subtypes when added to R-CHOP (PHOENIX subgroup analysis, Wilson et al. Cancer Cell 2021). Not formally approved as biomarker-selected indication in DLBCL; basket trials ongoing.R-CHOP + ibrutinib (off-label, MCD/genetically-selected)
pola-R-CHP (1L; POLARIX — not MYD88-selected but consider)
CAR-T axi-cel / liso-cel (R/R)
  • SRC-NCCN-BCELL-2025
  • SRC-ESMO-DLBCL-2024

Treatment options (2 tracks)

Standard plan
★ DEFAULT
Indication
IND-DLBCL-1L-RCHOP
Regimen
Rituximab + CHOP (R-CHOP), 6 cycles
Drugs + NSZU
  • Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 of each 21-day cycle · IV ✓ NSZU covered
  • Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 750 mg/m² · IV day 1 of each 21-day cycle · IV ⚠ NSZU — not for this indication
  • Doxorubicin (DRUG-DOXORUBICIN) 50 mg/m² · IV day 1 of each 21-day cycle · IV ✓ NSZU covered
  • Vincristine (DRUG-VINCRISTINE) 1.4 mg/m² (capped at 2 mg total) · IV day 1 of each 21-day cycle · IV ⚠ NSZU — not for this indication
  • Prednisone (DRUG-PREDNISONE) 100 mg · PO days 1-5 of each 21-day cycle · PO ⚠ NSZU — not for this indication
Supportive care
SUP-PJP-PROPHYLAXIS, SUP-TLS-PROPHYLAXIS, SUP-ANTIEMETIC-PREMED
Hard contraindications
CI-HBV-NO-PROPHYLAXIS, CI-LVEF-LOW-FOR-ANTHRACYCLINE
Reason
Engine default per algorithm ALGO-DLBCL-1L: {'step': 3, 'outcome': False, 'branch': {'result': 'IND-DLBCL-1L-RCHOP'}, 'fired_red_flags': [], 'winner_red_flag': None}
Aggressive plan
Indication
IND-DLBCL-1L-POLA-R-CHP
Regimen
Polatuzumab vedotin + Rituximab + CHP (Pola-R-CHP), 6 cycles + 2× rituximab
Drugs + NSZU
  • Polatuzumab vedotin (DRUG-POLATUZUMAB-VEDOTIN) 1.8 mg/kg · IV day 1 of each 21-day cycle, cycles 1-6 · IV ✗ Not registered in UA
  • Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 of each 21-day cycle, cycles 1-8 (last 2 cycles rituximab-only) · IV ✓ NSZU covered
  • Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 750 mg/m² · IV day 1 of each 21-day cycle, cycles 1-6 · IV ⚠ NSZU — not for this indication
  • Doxorubicin (DRUG-DOXORUBICIN) 50 mg/m² · IV day 1 of each 21-day cycle, cycles 1-6 · IV ✓ NSZU covered
  • Prednisone (DRUG-PREDNISONE) 100 mg · PO days 1-5 of each 21-day cycle, cycles 1-6 · PO ⚠ NSZU — not for this indication
Supportive care
SUP-PJP-PROPHYLAXIS, SUP-TLS-PROPHYLAXIS, SUP-ANTIEMETIC-PREMED
Hard contraindications
CI-HBV-NO-PROPHYLAXIS, CI-LVEF-LOW-FOR-ANTHRACYCLINE, CI-BORTEZOMIB-SEVERE-NEUROPATHY
Reason
Alternative track presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks
IDNamePriorityCategoryWhere to orderNeeded for
TEST-BM-ASPIRATEBone Marrow AspirateCriticalhistology—all tracks
TEST-BM-TREPHINEBone Marrow TrephineCriticalhistology—all tracks
TEST-CBCComplete Blood Count with DifferentialCriticallab—all tracks
TEST-CD20-IHCCD20 ImmunohistochemistryCriticalhistologyCSD Lab ✓ (code TBC)all tracks
TEST-CMPComprehensive Metabolic PanelCriticallab—all tracks
TEST-FISH-PANELFISH (Fluorescence In Situ Hybridization)CriticalgenomicCSD Lab ✓ (code TBC)all tracks
TEST-FLOW-CYTOMETRYFlow CytometryCriticalhistologyCSD Lab ✓ (code TBC)all tracks
TEST-HBV-SEROLOGYHepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs)Criticallab—all tracks
TEST-HCV-ANTIBODYHCV AntibodyCriticallab—all tracks
TEST-HIV-SEROLOGYHIV Antibody/AntigenCriticallab—all tracks
TEST-LDHLactate DehydrogenaseCriticallab—all tracks
TEST-LFTLiver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)Criticallab—all tracks
TEST-LN-EXCISIONAL-BIOPSYExcisional LN BiopsyCriticalhistology—all tracks
TEST-PREGNANCYBeta-HCGCriticallab—all tracks
TEST-B2-MICROGLOBULINBeta-2 MicroglobulinStandardlab—all tracks
TEST-ECHOEchocardiographyStandardimaging—all tracks
TEST-PET-CTFDG PET/CT (whole body)Standardimaging—all tracks

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track
  • Age-adjusted IPI ≥2 in patient <60 yo — high-risk young-adult DLBCL; supports DA-EPOCH-R consideration over R-CHOP per CALGB 50303 / Wilson and AYA-DLBCL seriesRF-AAIPI-HIGH
  • DLBCL with International Prognostic Index ≥2 — selects intensified Pola-R-CHP over R-CHOP per POLARIX evidenceRF-DLBCL-HIGH-IPI
  • High-risk biology in DLBCL NOS: double-expressor (MYC + BCL2 by IHC, no rearrangement), TP53 mutation, or non-GCB cell-of-origin in elderly / high-IPI context. Distinct from HGBL "double-hit" which is its own entity (DIS-HGBL-DH) — but double-expressor remains DLBCL NOS and shifts toward intensified backbone. RF-DLBCL-HIGH-RISK-BIOLOGY
  • DLBCL with International Prognostic Index 4-5 (high risk) — supports Pola-R-CHP intensification per POLARIX and triggers CNS-prophylaxis discussion via CNS-IPIRF-IPI-HIGH

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
  • 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
  • Severe pre-existing peripheral neuropathy is an absolute contraindication to bortezomib — therapy will likely worsen the neuropathy to a disabling and often permanent extent.CI-BORTEZOMIB-SEVERE-NEUROPATHY

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-DLBCL-1L-RCHOP)
  • Do not start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ — risk of fatal reactivation is significantly elevated on anti-CD20.
  • Do not prescribe without baseline LVEF ≥50% — anthracyclines are cardiotoxic; cardiomyopathy is often irreversible.
  • Do not ignore CNS-IPI — for patients with CNS-IPI ≥4 or high-risk anatomic sites (testicles, breasts, kidneys/adrenals, paranasal sinuses) add CNS prophylaxis (HD-MTX intercalated).
  • Do not skip the fertility preservation discussion in patients of reproductive age — cyclophosphamide causes azoospermia + amenorrhea.
  • Do not give vincristine intrathecally — FATAL. WHO/FDA require IV mini-bag packaging.
  • Do not escalate dose with febrile neutropenia without G-CSF — G-CSF prophylaxis for high-risk patients (age >65, prior cytopenia, advanced disease).
Aggressive plan (IND-DLBCL-1L-POLA-R-CHP)
  • Do not prescribe without a verified funding pathway — daratumumab... sorry, polatuzumab is not NSZU-reimbursed; the patient must be informed BEFORE being offered.
  • Do not start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ — anti-CD20 reactivation risk is not reduced by polatuzumab.
  • Do not prescribe without baseline LVEF ≥50% — anthracycline cardiotoxicity is the same as with R-CHOP.
  • Do not ignore pre-existing peripheral neuropathy — polatuzumab MMAE causes neuropathy; Grade ≥2 baseline = absolute CI.
  • Do not skip CNS prophylaxis if CNS-IPI ≥4 — same risk as with R-CHOP.
  • Do not use with concomitant strong CYP3A4 inhibitor without monitoring — increased neuropathy + myelosuppression.

Monitoring schedule

Monitoring schedule by treatment phase

Standard plan · MON-R-CHOP-REGIMEN

PhaseWindowTestsCheckpoints
baselineWithin 2 weeks before cycle 1TEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH, TEST-B2-MICROGLOBULIN, TEST-HBV-SEROLOGY, TEST-HCV-ANTIBODY, TEST-HIV-SEROLOGY, TEST-PET-CT, TEST-LN-EXCISIONAL-BIOPSY, TEST-FLOW-CYTOMETRY, TEST-CD20-IHC, TEST-ECHO, TEST-PREGNANCY, TEST-BM-ASPIRATE, TEST-BM-TREPHINE
  • Confirm CD20+ DLBCL histology; rule out double-hit (FISH for MYC/BCL2/BCL6)
  • Confirm HBV status + entecavir prophylaxis plan if HBsAg+ or anti-HBc+
  • Baseline LVEF ≥50% before doxorubicin
  • IPI calculation documented (age, ECOG, LDH, stage, extranodal sites)
  • CNS-IPI calculation if anatomic risk sites or composite score concerning
  • Fertility preservation discussion (sperm banking / oocyte cryo) for childbearing-age
on_treatmentDay 1 of every 21-day cycleTEST-CBC, TEST-CMP, TEST-LFT
  • ANC ≥1500 + platelets ≥100K before each cycle (delay or G-CSF if not)
  • Neuropathy grade documented (CTCAE) — vincristine modification if ≥2
  • LVEF re-check after cumulative doxorubicin ~300 mg/m²
interim_response_assessmentAfter cycles 2-4 (interim PET-CT)TEST-PET-CT, TEST-LDH
  • Lugano response criteria + Deauville score
  • If Deauville 4-5 with mass progression → consider salvage or trial
end_of_treatmentAfter cycle 6 (within 6-8 weeks)TEST-PET-CT, TEST-CBC, TEST-CMP, TEST-LDH
  • Confirm CR vs PR vs SD vs PD by Lugano/Deauville
  • Begin survivorship plan: cardiac surveillance schedule, vaccination catch-up, second-cancer screening
follow_up_shortEvery 3 months × 2 years post-treatmentTEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH
  • Surveillance for relapse (~40% relapse risk by 2 years overall)
  • HBV reactivation monitoring continues for 12 months post anti-CD20
follow_up_longEvery 6 months years 3-5, then annuallyTEST-CBC, TEST-LFT, TEST-ECHO
  • Late cardiomyopathy screening (LVEF) annually if cumulative dox >300
  • Annual second-malignancy screening (skin, breast, etc. age-appropriate)

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Baseline
Within 2 weeks before cycle 1
Induction · Rituximab + CHOP (R-CHOP), 6 c
21-day cycles × 6 (with consideration of 2-month interim PET-CT after cycles 2-4)
Response assessment
After cycles 2-4 (interim PET-CT)
Follow-up
Every 3 months × 2 years post-treatment

Aggressive plan

Baseline
Within 2 weeks before cycle 1
Induction · Polatuzumab vedotin + Rituxima
21-day cycles × 6 (Pola-R-CHP) + 2× rituximab consolidation (cycles 7-8)
Response assessment
After cycles 2-4 (interim PET-CT)
Follow-up
Every 3 months × 2 years post-treatment

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-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-IPI, 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

Skill catalog (3/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
Specialistskill_idVersionLast reviewedSign-offsDomain
Cellular therapy specialist (CAR-T)cellular_therapy_specialistv0.1.02026-04-250cellular_therapy
Clinical pharmacistclinical_pharmacistv0.1.02026-04-250clinical_pharmacy
Hematologist / oncohematologisthematologistv0.1.02026-04-250hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)hematopathologistv0.1.02026-04-250hematopathology
Infectious disease / hepatologyinfectious_disease_hepatologyv0.1.02026-04-250infectious_diseases
Medical oncologist (solid-tumor chemotherapist)medical_oncologistv0.1.02026-04-250solid_oncology
Molecular geneticist / molecular oncologistmolecular_geneticistv0.1.02026-04-250molecular_oncology
Palliative carepalliative_carev0.1.02026-04-250palliative_care
Pathologist (general)pathologistv0.1.02026-04-250pathology
Primary care / family physicianprimary_carev0.1.02026-04-250primary_care
Psycho-oncologistpsychologistv0.1.02026-04-250psychosocial
Radiation oncologistradiation_oncologistv0.1.02026-04-250radiation_oncology
Radiologistradiologistv0.1.02026-04-250diagnostic_imaging
Social worker / case managersocial_worker_case_managerv0.1.02026-04-250psychosocial
Surgical oncologistsurgical_oncologistv0.1.02026-04-250surgical_oncology
Transplant specialist (BMT)transplant_specialistv0.1.02026-04-250cellular_therapy

Sources cited

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).
OptionUA registrationNSZUCost orientationAccess pathway
Standard plan
Rituximab + CHOP (R-CHOP), 6 cycles (REG-R-CHOP)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Aggressive plan
Polatuzumab vedotin + Rituximab + CHP (Pola-R-CHP), 6 cycles + 2× rituximab (REG-POLA-R-CHP)
1/5 component drug(s) not registered in Ukraine +1
✗ not registered✗ out-of-pocket₴-? — verify pathwaynot recorded

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.

plan_id: PLAN-BMA-MYD88_L265P_DLBCL_NOS-V1 | version: 1 | generated: 2026-05-04T14:13:16.640583+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.