Tisagenlecleucel
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | DRUG-TISAGENLECLEUCEL |
|---|---|
| Тип | Препарат |
| Синоніми | CTL019Kymriahtisa-celТисагенлеклеуцел |
| Статус | переглянуто 2026-04-25 | очікує клінічного підпису |
| Хвороби | DIS-B-ALL |
| Джерела | SRC-NCCN-BCELL-2025 |
Дані про препарат
| Клас | CD19-directed autologous CAR-T cell therapy (4-1BB costimulation) |
|---|---|
| Механізм дії | Autologous T cells genetically modified ex vivo with lentiviral vector encoding chimeric antigen receptor (CAR) targeting CD19, with 4-1BB costimulatory domain (CD137) and CD3-zeta signaling domain. After lymphodepleting fludarabine + cyclophosphamide conditioning, single IV infusion → in vivo expansion + sustained cytotoxicity against CD19+ B-cell malignancies. Approved for R/R B-ALL ≤25 years (ELIANA) and R/R DLBCL adult (JULIET). |
| Типове дозування | Single IV infusion (not weight-based per se): 0.2 to 5.0 × 10⁶ CAR-positive viable T cells per kg for patients ≤50 kg; 0.1 to 2.5 × 10⁸ CAR-positive viable T cells (not weight-based) for patients >50 kg. Preceded by lymphodepleting conditioning: fludarabine 30 mg/m² IV daily × 4 days + cyclophosphamide 500 mg/m² IV daily × 2 days. Single infusion; no maintenance. |
| Зареєстровано в Україні | False |
| Відшкодовується НСЗУ | False |
| Остання перевірка для України | 2026-04-27 |
Застереження
- Cytokine release syndrome (CRS) — Grade ≥3 ~46% in ELIANA; tocilizumab + ICU support mandatory
- Immune effector cell-associated neurotoxicity syndrome (ICANS) — Grade ≥3 ~13%
- REMS / FACT-JACIE accreditation required for administration
Нотатки
Pivotal: ELIANA (Maude et al., NEJM 2018) — single-arm phase-2 in R/R B-ALL ages 3-21 (later expanded to ≤25); ORR 81%; CR/CRi 60%; MRD-negativity in CR/CRi 100%; 12-month EFS 50%, OS 76%. FDA approval Aug 2017 (first FDA-approved CAR-T). EMA Aug 2018. CRITICAL: REMS / FACT-JACIE-accredited center required; tocilizumab on-site (≥2 doses) before infusion mandatory; CNS exclusion (CNS-2/3 symptomatic) per registration. Ukraine: NOT registered, NO domestic manufacturing — international referral (Israel / Poland / Germany / Spain) required, USD 350-500K all-in. Adult (>25) DLBCL CAR-T variants (axi-cel, liso-cel, brexu-cel for B-ALL adults) are separate products with distinct costimulatory designs (CD28 vs 4-1BB) and AE profiles (axi-cel CD28 → faster, more severe CRS / ICANS; tisa-cel 4-1BB → slower onset, more durable persistence). Ukraine: NOT registered — no domestic CAR-T manufacturing capacity; access only via cross- border to EBMT/JACIE-accredited EU centers (Charité, Karolinska, Saint-Louis) under "Лікування за кордоном" (наказ МОЗ 988). All-in cost USD 350-500K including manufacturing, lymphodepletion, ICU support, post-CAR-T B-cell-aplasia management.
Де використовується
Regimens
REG-TISAGENLECLEUCEL-B-ALL- Tisagenlecleucel CD19 CAR-T for R/R B-ALL ≤25 years