OpenOnco · Treatment Plan

Treatment plan — DIS-MDS-HR

PLAN-BMA-IDH1_R132H_MDS_HR-V1 · v1 · 2026-05-04

Patient

BMA-IDH1_R132H_MDS_HR · Algorithm: ALGO-MDS-HR-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-IDH-MUTATION	IDH1 R132H	IIA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Better Outcome) SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	IDH1 R132 in MDS — ivosidenib monotherapy active (DiNardo et al. JCO 2021 — ORR 75% MDS, CR 38%). Ivosidenib + azacitidine combos in trial. Off-label NCCN-supported.	ivosidenib (off-label MDS) ivosidenib + azacitidine (trial)	SRC-ESMO-MDS-2021
BIO-IDH-MUTATION	IDH2 R140Q	IIA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Better Outcome) SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	IDH2 R140Q in MDS — enasidenib monotherapy active in MDS (NCT01915498, DiNardo et al. Blood 2018). IDH-mut MDS often progresses to AML; IDH2i can delay transformation. Not yet on full FDA MDS label (off-label use NCCN-supported).	enasidenib (off-label MDS)	SRC-ESMO-MDS-2021 SRC-IPSS-M-BERNARD-2022
BIO-IDH-MUTATION	IDH2 R172K	IIA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Better Outcome) SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	IDH2 R172K in MDS — same enasidenib rationale as R140Q.	enasidenib (off-label MDS)	SRC-ESMO-MDS-2021

Treatment options (2 tracks)

Standard plan

★ DEFAULT

Indication

IND-MDS-HR-1L-AZA

Regimen

Azacitidine (MDS-HR 1L)

Drugs + NSZU

Azacitidine (DRUG-AZACITIDINE) 75 mg/m²/day · SC days 1-7 of each 28-day cycle (or 5-2-2 schedule for outpatient convenience) · SC ✓ NSZU covered

Supportive care

SUP-HBV-PROPHYLAXIS

Reason

Engine default per algorithm ALGO-MDS-HR-1L: {'step': 4, 'outcome': False, 'branch': {'result': 'IND-MDS-HR-1L-AZA'}, 'fired_red_flags': [], 'winner_red_flag': None}

Aggressive plan

Indication

IND-MDS-HR-1L-VEN-AZA

Regimen

Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule

Drugs + NSZU

Venetoclax (DRUG-VENETOCLAX) Cycle 1 ramp: day 1 = 100 mg, day 2 = 200 mg, day 3 = 400 mg → days 4-28 = 400 mg PO daily; subsequent cycles = 400 mg daily continuously · PO daily; reduce to ~70-100 mg if combined with strong CYP3A4 inhibitor (posaconazole) · PO ⚠ NSZU — not for this indication
Azacitidine (DRUG-AZACITIDINE) 75 mg/m²/day · SC or IV days 1-7 of each 28-day cycle · SC ✓ NSZU covered

Supportive care

SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS

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-BM-ASPIRATE	Bone Marrow Aspirate	Critical	histology	—	all tracks
TEST-BM-TREPHINE	Bone Marrow Trephine	Critical	histology	—	all tracks
TEST-CBC	Complete Blood Count with Differential	Critical	lab	—	all tracks
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-COAG-PANEL	Coagulation Panel	Critical	lab	—	all tracks
TEST-FISH-PANEL	FISH (Fluorescence In Situ Hybridization)	Critical	genomic	CSD Lab ✓ (code TBC)	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-KARYOTYPE	Karyotype	Critical	genomic	CSD Lab ✓ (code TBC)	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-NGS-MYELOID-PANEL	Myeloid NGS Panel	Critical	genomic	CSD Lab ✓ (code TBC)	all tracks
TEST-PERIPHERAL-SMEAR	Peripheral Blood Smear	Critical	lab	CSD Lab ✓ (code TBC)	all tracks
TEST-B12-FOLATE	B12 + Folate	Standard	lab	—	standard
TEST-CMV-SEROLOGY	CMV IgG/IgM	Standard	lab	—	standard
TEST-ECHO	Echocardiography	Standard	imaging	—	desired (aggressive, standard)
TEST-IRON-PANEL	Iron Panel	Standard	lab	—	standard
TEST-RETICULOCYTE	Reticulocyte Count	Standard	lab	—	standard
TEST-URIC-ACID	Serum Uric Acid	Standard	lab	—	aggressive

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

MDS patient elderly or frail (age ≥80, ECOG ≥3, life expectancy <2 years, multiple comorbidities) where best supportive care or low-intensity HMA is preferred over alloHCT or intensive disease modificationRF-MDS-FRAILTY-AGE
MDS patient with organ dysfunction limiting therapy: ECOG ≥3, severe renal impairment (CrCl <30), hepatic dysfunction (bilirubin >3× ULN), or cardiac dysfunction (LVEF <40%, NYHA III-IV)RF-MDS-ORGAN-DYSFUNCTION
MDS with TP53 mutation (mono- or biallelic) — distinct WHO 5th-ed entity with poor outcomes on HMA monotherapy and reduced alloHCT benefit; consideration of intensified / experimental therapy or palliative intentRF-MDS-TP53-MUTATION
MDS progressing to AML (≥20% blasts) or accelerated MDS-IB2 with rapid progression on HMA — switch to AML algorithm or escalate to ven+aza / intensive chemo + alloHCT bridgeRF-MDS-TRANSFORMATION-PROGRESSION
MDS-HR patient transplant-eligible: age <70-75 (per local practice), HCT-CI ≤4, adequate organ function, donor available — initiate alloHCT donor search at HMA initiation, not at HMA failureRF-MDS-TRANSPLANT-ELIGIBLE

CONTRA-AGGRESSIVE

Hard contraindications to escalation

What NOT to do

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

Standard plan (IND-MDS-HR-1L-AZA)

Do not skip pre-HMA HBV screening + prophylaxis — HMA-associated HBV reactivation has been described.
Do not stop HMA before cycle 6 without overt progression — response is often late (cycles 4-6).
Do not expect CR — most patients achieve hematologic improvement without CR; this has clinical value.
Do not skip donor search in parallel with HMA for transplant-eligible — search window 3-6 months.
Do not prescribe ven+aza in MDS-HR as 1L without trial / clinical justification — only extrapolation from VIALE-A AML, without HR-MDS-specific phase 3.

Aggressive plan (IND-MDS-HR-1L-VEN-AZA)

Do not skip venetoclax 3-day ramp + TLS prophylaxis.
Do not use ven+aza in patients non-fit for alloHCT (standard aza alone is an alternative with a better toxicity profile).
Do not expect phase-3 validation — VERONA and other trials in progress; current use is off-label.
Do not skip informed consent regarding off-label use and uncertainty about OS benefit.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Azacitidine (MDS-HR 1L)

28-day cycles × Continue ≥6 cycles before declaring failure (response often delayed to cycles 4-6); continue until progression / unacceptable toxicity in responders

Aggressive plan

Induction · Venetoclax + Azacitidine (AML,

28-day cycles × Continue until progression / unacceptable toxicity (median ~12 cycles in VIALE-A; ~25-30% achieve durable remission)

MDT brief

Skills (recommended) — for consideration (1)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

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

Unevaluated RedFlags: RF-IPSS-M-HIGH, RF-IPSS-R-VERY-HIGH, RF-MDS-FRAILTY-AGE, RF-MDS-HIGH-RISK-IPSS, RF-MDS-INFECTION-SCREENING, RF-MDS-ORGAN-DYSFUNCTION, RF-MDS-TP53-MUTATION, RF-MDS-TRANSFORMATION-PROGRESSION, RF-MDS-TRANSPLANT-ELIGIBLE

Skill catalog (1/16 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-ESMO-MDS-2021: Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2021)
SRC-IPSS-M-BERNARD-2022: Molecular International Prognostic Scoring System for Myelodysplastic Syndromes (2022)
SRC-NCCN-AML-2025: NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia (v.X.2025)
SRC-VIALE-A-DINARDO-2020: Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia (2020)

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 Azacitidine (MDS-HR 1L) (REG-AZA-MDS-HR)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule (REG-VEN-AZA-AML)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary

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

plan_id: PLAN-BMA-IDH1_R132H_MDS_HR-V1 | version: 1 | generated: 2026-05-04T14:13:16.612972+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.