Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
VERIFIED-MM-L3-MM_3L_ISA_KD · Algorithm: ALGO-MM-3L
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. |
Primary current-line option
- Indication
- IND-MM-3L-ISA-KD
- Regimen
- Isatuximab + Carfilzomib + Dexamethasone (Isa-Kd), 28-day cycles
- Drugs + NSZU
- Isatuximab (DRUG-ISATUXIMAB) 10 mg/kg IV · Days 1, 8, 15, 22 (cycle 1); days 1, 15 (cycles 2+) · IV ✗ Not registered in UA
- Carfilzomib (DRUG-CARFILZOMIB) 20 mg/m² IV days 1-2 cycle 1 (ramp-up), then 56 mg/m² IV · Days 1, 2, 8, 9, 15, 16 of each 28-day cycle (56 mg/m² from day 8 cycle 1) · IV ⚠ NSZU — not for this indication
- Dexamethasone (DRUG-DEXAMETHASONE) 20 mg IV or PO · Days 1, 2, 8, 9, 15, 16, 22, 23 of each 28-day cycle · IV ✓ NSZU covered
- Supportive care
- SUP-HSV-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-MM-VTE-PROPHYLAXIS, SUP-MM-BONE-PROTECTION
- Reason
- Primary current-line option selected by ALGO-MM-3L at step 3.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-MM-4L-TECLISTAMAB
- Regimen
- Teclistamab BCMA × CD3 bispecific (with step-up dosing) — continuous SC weekly
- Drugs + NSZU
- Teclistamab (DRUG-TECLISTAMAB) Step-up: 0.06 mg/kg SC day 1, 0.3 mg/kg SC day 4, 1.5 mg/kg SC day 7 (≥48h between doses, inpatient observation). Full dose 1.5 mg/kg SC weekly thereafter.
· Weekly SC continuous (after step-up); transition to q2-weekly after ≥6 mo sustained ≥VGPR (per protocol amendment) · SC ✗ Not registered in UA
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-IVIG-HYPOGAMMA
- Hard contraindications
- CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB
- Reason
- Current-line alternative 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-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-FREE-LIGHT-CHAINS | Serum Free Light Chains | 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 | — | aggressive |
| TEST-HIV-SEROLOGY | HIV Antibody/Antigen | Critical | lab | — | aggressive |
| 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 | — | aggressive |
| TEST-SPEP-UPEP | SPEP / UPEP with IFE | Critical | lab | — | all tracks |
| TEST-WHOLE-BODY-MRI | Whole-Body MRI | Critical | imaging | — | desired (aggressive, standard) |
| TEST-B2-MICROGLOBULIN | Beta-2 Microglobulin | Standard | lab | — | all tracks |
| TEST-CMV-SEROLOGY | CMV IgG/IgM | Standard | lab | — | aggressive |
| TEST-DAT-COOMBS | Direct Antiglobulin Test | Standard | lab | — | standard |
| TEST-ECHO | Echocardiography | Standard | imaging | — | all tracks |
| TEST-IMMUNOGLOBULINS | Quantitative Immunoglobulins | Standard | lab | — | all tracks |
| TEST-EBV-SEROLOGY | EBV Antibody Panel | Desired | lab | — | aggressive |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Multiple myeloma high-risk cytogenetics: any of t(4;14), t(14;16), t(14;20), del(17p)/TP53 loss, gain or amplification of 1q21 by interphase FISH on CD138-enriched plasma cells
Primary determinant for selecting quadruplet (D-VRd) over triplet (VRd) in transplant-eligible newly-diagnosed MM. R2-ISS captures most of these abnormalities; gain 1q21 is graded by copy count (≥4 copies = amp1q carries higher risk than…
RF-MM-HIGH-RISK-CYTOGENETICSSRC-NCCN-MM-2025SRC-ESMO-MM-2023 - Multiple myeloma with significant renal dysfunction: CrCl <60 mL/min or serum creatinine >177 µmol/L (>2 mg/dL) attributable to myeloma kidney
Direction "investigate" — triggers lenalidomide dose adjustment in BOTH VRd and D-VRd and demands further workup (24-hr urine, kidney biopsy in selected cases) to distinguish myeloma kidney from other causes. Does not shift the…
RF-MM-RENAL-DYSFUNCTIONSRC-NCCN-MM-2025SRC-ESMO-MM-2023
CONTRA-AGGRESSIVE
Hard contraindications to escalation
- Alemtuzumab causes profound, prolonged CD4+ T-cell depletion (median recovery 9-12 months). Active uncontrolled infection at baseline becomes life-threatening once cellular immunity collapses. HIV-positive status is itself an absolute contraindication — alemtuzumab on top of HIV immunosuppression has unacceptable infectious mortality.
CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-MM-3L-ISA-KD)
- Do not use with prior carfilzomib exposure — IKEMA enrolled carfilzomib-naive patients; efficacy and safety on re-challenge not established by this trial.
- Do not use in ECOG PS ≥3 — patients with poor performance status were excluded from IKEMA; response and toxicity unpredictable.
- Do not prescribe without baseline ECG + ECHO + controlled hypertension — carfilzomib has 5-7% rate of cardiac AE.
- Do not skip baseline DAT/Coombs + red-cell phenotyping BEFORE first isatuximab — anti-CD38 interferes with crossmatch for months.
- Do not start without HBV screening + entecavir prophylaxis in HBsAg+ or anti-HBc+.
- Do not skip IV hydration (250-500 mL pre/post) for the first carfilzomib — TLS + AKI risk highest cycle 1.
- Do not confirm plan without verified funding pathway — neither isatuximab nor carfilzomib are reimbursed by NSZU.
- Do not escalate carfilzomib to full dose (56 mg/m²) without cycle-1 step-up (20 mg/m² days 1-2).
Aggressive plan (IND-MM-4L-TECLISTAMAB)
- Do not start outside inpatient settings — step-up doses require ≥48h hospital observation for CRS surveillance.
- Do not skip IVIG for IgG <400 — universal hypogammaglobulinemia + infectious burden is a leading cause of mortality.
- Do not skip PJP + HSV/VZV prophylaxis — opportunistic infection risk is very high.
- Do not continue with active uncontrolled infection — pause until resolution is mandatory.
- Do not start without on-site tocilizumab (≥2 doses) for emergency CRS rescue.
- Do not prescribe with baseline ECOG ≥3 — clinical trial excluded; on-treatment mortality very high in frail patients.
- Do not forget about live vaccines — contraindicated during and ≥6 months after treatment.
- Do not confirm plan without international referral pathway + funding — drug not available in Ukraine.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Isatuximab + Carfilzomib + Dexamethasone (Isa-Kd), 28-day cycles
28-day cycles × Until progression or unacceptable toxicity
Aggressive plan
Induction · Teclistamab BCMA × CD3 bispecific (with step-up dosing) — continuous SC weekly
7-day cycles × Continuous until progression or unacceptable toxicity
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (2 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. |
Skills (recommended) — for consideration (1)
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: 0/0 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ISS-1, RF-ISS-3, RF-MM-BCMA-EXPRESSION-POS, RF-MM-CD38-EXPRESSION-DARA-CANDIDATE, RF-MM-CORD-COMPRESSION, RF-MM-FRAILTY-AGE, RF-MM-HIGH-RISK-CYTOGENETICS, RF-MM-HYPERCALCEMIA, RF-MM-HYPERVISCOSITY, RF-MM-INFECTION-SCREENING, RF-MM-RENAL-DYSFUNCTION, RF-MM-T11-14-ACTIONABLE, RF-MM-TRANSFORMATION-PROGRESSION, RF-R-ISS-3-HIGH-RISK
Technical MDT skill metadata (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-EHA-EMN-MM-2025: EHA-EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma (2025)
- SRC-ESMO-MM-2023: ESMO Clinical Practice Guideline on Multiple Myeloma (2023)
- SRC-IKEMA-MOREAU-2021: Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial (2021)
- SRC-MAJESTEC-1-MOREAU-2022: Teclistamab in Relapsed or Refractory Multiple Myeloma (2022)
- SRC-NCCN-MM-2025: NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma (v.X.2025)
Experimental options (clinical trials)
Last synced: 2026-09-09 · 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 Isatuximab + Carfilzomib + Dexamethasone (Isa-Kd), 28-day cycles (REG-ISA-KD-MM-3L) 1/3 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Teclistamab BCMA × CD3 bispecific (with step-up dosing) — continuous SC weekly (REG-TECLISTAMAB) 1/1 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: 2026-09-09.