Lisocabtagene maraleucel
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | DRUG-LISOCABTAGENE-MARALEUCEL |
|---|---|
| Тип | Препарат |
| Синоніми | BreyanziJCAR017liso-celЛісокабтаген маралейцел |
| Статус | переглянуто 2026-04-27 | очікує клінічного підпису |
| Хвороби | Не вказано |
| Джерела | SRC-ESMO-DLBCL-2024 SRC-NCCN-BCELL-2025 SRC-TRANSCEND-NHL-001-ABRAMSON-2020 |
Дані про препарат
| Клас | CD19-directed autologous CAR-T cell therapy (4-1BB costimulation; defined CD4:CD8 1:1 composition) |
|---|---|
| Механізм дії | Autologous T cells transduced with a lentiviral vector encoding a CAR with anti-CD19 single-chain variable fragment (FMC63), 4-1BB costimulatory domain, and CD3-zeta activation domain. Distinguishing feature is administration of a defined 1:1 ratio of CD4+ and CD8+ CAR-T cells (separately manufactured, then combined), which is hypothesized to deliver more predictable expansion kinetics and a more favorable CRS/ICANS profile vs CD28-based products. Lymphodepleting fludarabine + cyclophosphamide conditioning precedes a single IV infusion. Approved by FDA Feb 2021 and EMA April 2022 for relapsed/ refractory large B-cell lymphoma (TRANSCEND-NHL-001), expanded in 2022 to 2L (TRANSFORM trial), and in 2024 to relapsed/refractory CLL/SLL (TRANSCEND-CLL-004) and to relapsed/refractory follicular lymphoma (TRANSCEND-FL). |
| Типове дозування | Single IV infusion, target dose 100 × 10⁶ CAR-positive viable T cells (50-110 × 10⁶ in 1:1 CD4:CD8 ratio). Administered 2-7 days after lymphodepleting conditioning: cyclophosphamide 300 mg/m² IV daily × 3 days + fludarabine 30 mg/m² IV daily × 3 days (days -5 to -3). Tocilizumab on-site (≥2 doses) before infusion is mandatory per REMS. Single infusion; no maintenance. Bridging therapy may be used during the 3-5 week manufacturing window. Renal adjustment: fludarabine 24 mg/m² × 3 d if CrCl 30-69 mL/min; both agents held if CrCl <30 mL/min (consider alternative conditioning per institutional protocol). Hold infusion if active uncontrolled infection, severe organ dysfunction, or ANC <1,000/µL... |
| Зареєстровано в Україні | False |
| Відшкодовується НСЗУ | False |
| Остання перевірка для України | 2026-04-27 |
Застереження
- Cytokine release syndrome (CRS) — Grade ≥3 ~2% in TRANSCEND-NHL-001 (any-grade ~42%); markedly lower than CD28 CAR-Ts
- Immune effector cell-associated neurotoxicity syndrome (ICANS) — Grade ≥3 ~10% (any-grade ~30%)
- Hemophagocytic lymphohistiocytosis / macrophage activation syndrome (HLH/MAS)
- Prolonged cytopenias and B-cell aplasia / hypogammaglobulinemia
- Secondary T-cell malignancies (FDA class boxed warning, 2024)
- REMS / FACT-JACIE accreditation required for administration
Нотатки
Pivotal: TRANSCEND-NHL-001 (Abramson et al., Lancet 2020) — 269 R/R LBCL patients ≥2 prior lines, ORR 73%, CR 53%, median DoR 23.1 months; Grade ≥3 CRS only 2% — markedly lower than axi-cel (~13%) and tisa-cel (~22%). TRANSFORM (Lancet 2022) moved liso-cel to 2L for primary- refractory / ≤12-month relapse DLBCL (superior EFS vs salvage + autoSCT). 2024 expansions: TRANSCEND-CLL-004 in BTKi/venetoclax- refractory CLL; TRANSCEND-FL in heavily pretreated FL. Differentiator vs axi-cel: 4-1BB costimulation + defined CD4:CD8 1:1 ratio → slower-onset, lower-grade CRS/ICANS (more outpatient-feasible at experienced centers). Ukraine: NOT registered, NO domestic CAR-T manufacturing. Access only via cross-border referral under "Лікування за кордоном" (наказ МОЗ 988); all-in cost USD 410-450K including manufacturing, lymphodepletion, ICU support, and IVIG supplementation for B-cell aplasia.
Де використовується
Regimens
REGIMEN-LISOCEL-DLBCL-2L- Lisocabtagene maraleucel (liso-cel) CAR-T 2L for primary-refractory or early-relapse LBCL...REGIMEN-LISOCEL-DLBCL-3L- Lisocabtagene maraleucel (liso-cel) CAR-T for r/r LBCL ≥3L (TRANSCEND NHL 001)