Patient
COVERAGE-ADVSM-001 · Algorithm: ALGO-ADVSM-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 |
|---|
| No clinically actionable variants matched in this profile. |
| Biomarker | Status |
|---|
| BIO-KIT | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
Primary current-line option
- Indication
- IND-ADVSM-1L-MIDOSTAURIN
- Regimen
- Midostaurin monotherapy (advanced systemic mastocytosis, 1L alternative; D816V- or avapritinib-contraindicated)
- Drugs + NSZU
- Midostaurin (DRUG-MIDOSTAURIN) 100 mg PO BID with food · Continuous, until progression or unacceptable toxicity · PO ✓ NSZU covered
- Reason
- Primary current-line option selected by ALGO-ADVSM-1L at step 2.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-ADVSM-1L-AVAPRITINIB
- Regimen
- Avapritinib monotherapy (advanced systemic mastocytosis, 1L; KIT D816V+)
- Drugs + NSZU
- Avapritinib (DRUG-AVAPRITINIB) 200 mg PO once daily on empty stomach (≥1 h before / ≥2 h after food) · Continuous, until progression or unacceptable toxicity · PO ✗ Not registered in UA
- Reason
- Current-line alternative presented for HCP consideration
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-ADVSM-1L-MIDOSTAURIN)
- Do NOT use imatinib in KIT D816V advanced SM (intrinsic resistance) — imatinib is reserved for the rare FIP1L1-PDGFRA myeloid neoplasm with eosinophilia (separate entity).
- Do NOT continue midostaurin through gr ≥3 nausea/vomiting without antiemetic optimization + dose reduction (100 → 50 mg BID).
- Do NOT start midostaurin without baseline ECG — QT prolongation requires electrolyte correction + monitoring.
Standard plan (IND-ADVSM-1L-AVAPRITINIB)
- Do NOT use imatinib in KIT D816V advanced SM — intrinsic resistance (steric clash).
- Do NOT start avapritinib with platelets <50 ×10⁹/L — boxed warning; switch to midostaurin (alternative indication).
- Do NOT use avapritinib as monotherapy for SM-AHN — the AHN component (MDS / CMML / AML) needs its own histology-directed therapy.
- Do NOT skip baseline brain MRI — cerebral microbleed surveillance is part of the monitoring schedule.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · Midostaurin monotherapy (advanced systemic mastocytosis, 1L alternative; D816V- or avapritinib-contraindicated)
28-day cycles × Continuous until progression
Standard plan
Induction · Avapritinib monotherapy (advanced systemic mastocytosis, 1L; KIT D816V+)
28-day cycles × Continuous until progression
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (3 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 3 | molecular_geneticist | Specialist review | Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed. |
Skills (recommended) — for consideration (2)
- 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.
Data quality
Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.
- Biomarker coverage: 1/1 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ADVSM-KIT-D816V, RF-MASTOCYTOSIS-FRAILTY-AGE, RF-MASTOCYTOSIS-HIGH-RISK-BIOLOGY, RF-MASTOCYTOSIS-INFECTION-SCREENING, RF-MASTOCYTOSIS-ORGAN-DYSFUNCTION, RF-MASTOCYTOSIS-TRANSFORMATION-PROGRESSION
Technical MDT skill metadata (2/16 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-ESMO-AML-2020: Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2020)
- SRC-NCCN-SM-2025: NCCN Clinical Practice Guidelines — Systemic Mastocytosis (2025.v1)
- SRC-ONCOKB: OncoKB — Precision Oncology Knowledge Base (continuous (last verified 2026-04-25))
Experimental options (clinical trials)
Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-13.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT06748001 | Avapritinib Rollover Study | PHASE4 | RECRUITING | — | — | |
| NCT04996875 | (Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis | PHASE2 | RECRUITING | — | Surrogate endpoint only | |
Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.
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 |
|---|
| Aggressive plan Midostaurin monotherapy (advanced systemic mastocytosis, 1L alternative; D816V- or avapritinib-contraindicated) (REG-MIDOSTAURIN-ADVSM-1L) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Avapritinib monotherapy (advanced systemic mastocytosis, 1L; KIT D816V+) (REG-AVAPRITINIB-ADVSM-1L) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Trial · NCT06748001 Avapritinib Rollover Study No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04996875 (Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-13.