Patient
BMA-IDH1_R132H_MDS_LR · Algorithm: ALGO-MDS-LR-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) | |
| 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) | |
Treatment options (3 tracks)
- Indication
- IND-MDS-LR-1L-ESA
- Regimen
- ESA (epoetin alfa or darbepoetin) — MDS-LR symptomatic anemia 1L
- Drugs + NSZU
- Epoetin alfa / Darbepoetin alfa (DRUG-EPOETIN-ALFA) Epoetin alfa 60,000 IU SC weekly OR Darbepoetin 150-300 μg SC weekly (or 500 μg SC q3wk) · weekly SC; reassess at 8-12 weeks · SC ✓ NSZU covered
- Reason
- Engine default per algorithm ALGO-MDS-LR-1L: {'step': 4, 'outcome': False, 'branch': {'result': 'IND-MDS-LR-1L-ESA'}, 'fired_red_flags': [], 'winner_red_flag': None}
- Indication
- IND-MDS-LR-1L-LUSPATERCEPT
- Regimen
- Luspatercept (MDS-LR with RS or post-ESA failure)
- Drugs + NSZU
- Luspatercept (DRUG-LUSPATERCEPT) 1.0 mg/kg SC q3wk; titrate to 1.33 mg/kg then 1.75 mg/kg if no transfusion-burden reduction after 2 doses · every 3 weeks SC · SC ✗ Not registered in UA
- Reason
- Alternative track presented for HCP consideration
- Indication
- IND-MDS-LR-LENALIDOMIDE-DEL5Q
- Regimen
- Lenalidomide for del(5q) LR-MDS
- Drugs + NSZU
- Lenalidomide (DRUG-LENALIDOMIDE) 10 mg PO once daily on days 1-21 of 28-day cycle · Continuous cycles until loss of transfusion independence / progression / unacceptable toxicity · PO ✓ NSZU covered
- Hard contraindications
- CI-LENALIDOMIDE-PREGNANCY
- 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-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-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-PREGNANCY | Beta-HCG | Critical | lab | — | standard |
| TEST-B12-FOLATE | B12 + Folate | Standard | lab | — | all tracks |
| TEST-ECHO | Echocardiography | Standard | imaging | — | desired (standard) |
| TEST-ESR-CRP | ESR + CRP | Standard | lab | — | standard |
| TEST-IRON-PANEL | Iron Panel | Standard | lab | — | all tracks |
| TEST-RETICULOCYTE | Reticulocyte Count | Standard | lab | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- MDS with isolated del(5q) (or del(5q) plus one additional non-7 abnormality) — lenalidomide-responsive subgroup with ~67% RBC transfusion independence; favorable prognosisRF-MDS-DEL-5Q-ISOLATED
- MDS escalates from lower-risk to higher-risk classification by IPSS-R (high / very high, >4.5 points) or IPSS-M (High / Very High) — treatment intent shifts from cytopenia management to disease modification + alloHCT bridgingRF-MDS-HIGH-RISK-IPSS
- 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
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-LR-1L-ESA)
- Do not prescribe ESA at Hb >12 g/dL — boxed warning regarding thromboembolism + mortality.
- Do not continue ESA in the absence of response at 8-12 weeks — switch to luspatercept (if available) / lenalidomide / HMA.
- Do not skip iron studies + B12/folate before ESA — functional iron deficiency limits response.
- Do not skip IPSS-R / IPSS-M risk stratification — required to exclude MDS-HR.
- Do not prescribe lenalidomide without excluding del(5q) in MDS-LR — efficacy only in del(5q) context.
Aggressive plan (IND-MDS-LR-1L-LUSPATERCEPT)
- Do not expect a rapid response — luspatercept requires 8-12 weeks; do not stop earlier.
- Do not prescribe with uncontrolled HTN — luspatercept-induced HTN can be severe.
- Do not prescribe without VTE assessment — VTE risk is elevated (especially in β-thalassemia context; also MDS).
- Do not dose without weight — this is weight-based SC dosing.
- Do not skip IPSS-R / IPSS-M risk stratification.
Standard plan (IND-MDS-LR-LENALIDOMIDE-DEL5Q)
- Do not prescribe without cytogenetic confirmation of del(5q) — efficacy specific to del(5q) clones.
- Do not prescribe without REMS / Revlimid Risk Management Programme — drug is teratogenic; numerous birth defects have been documented.
- Do not skip pregnancy testing weekly for the first month, then monthly in women of childbearing potential.
- Do not prescribe concurrent ESA — additive VTE risk; choose one agent.
- Do not ignore TP53-status — TP53-mutated del(5q) MDS has significantly higher risk of AML transformation on lenalidomide; consider earlier alloHCT pathway.
- Do not skip VTE prophylaxis (aspirin 81-325 mg or LMWH) throughout the entire therapy.
- Do not continue without response — if no TI by 6 months, stop; consider alternative (luspatercept, imetelstat).
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · ESA (epoetin alfa or darbepoet
7-day cycles × Continue if response (Hb ≥1.5 g/dL rise or transfusion-independence achieved); discontinue if no response by 12 weeks
Aggressive plan
Induction · Luspatercept (MDS-LR with RS o
21-day cycles × Continue if transfusion-burden reduction; reassess at 24 weeks
Standard plan
Induction · Lenalidomide for del(5q) LR-MD
28-day cycles × Continue until loss of TI / progression / unacceptable toxicity; median TI duration >2 years per MDS-004
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)
Data quality
- Unevaluated RedFlags: RF-IPSS-M-HIGH, RF-MDS-DEL-5Q-ISOLATED, 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
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 | 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-COMMANDS-FENAUX-2020: Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes (2020)
- SRC-ESMO-MDS-2021: Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2021)
- SRC-MDS-004-FENAUX-2011: A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q (2011)
- SRC-NCCN-AML-2025: NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia (v.X.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 ESA (epoetin alfa or darbepoetin) — MDS-LR symptomatic anemia 1L (REG-ESA-MDS-LR) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Luspatercept (MDS-LR with RS or post-ESA failure) (REG-LUSPATERCEPT-MDS-LR) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Standard plan Lenalidomide for del(5q) LR-MDS (REG-LENALIDOMIDE-MDS-DEL5Q) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.