Ciltacabtagene autoleucel
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-CILTACABTAGENE-AUTOLEUCEL |
|---|---|
| Type | Drug |
| Aliases | CarvyktiJNJ-4528LCAR-B38Mcilta-celЦилтакабтаген аутолейцел |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | DIS-MM |
| Sources | SRC-CARTITUDE-1-BERDEJA-2021 SRC-ESMO-MM-2023 SRC-NCCN-MM-2025 |
Drug Facts
| Class | BCMA-directed autologous CAR-T cell therapy (4-1BB costimulation; dual-epitope binder) |
|---|---|
| Mechanism | Autologous T cells transduced with a lentiviral vector encoding a chimeric antigen receptor (CAR) that contains two BCMA-targeting heavy-chain-only variable domains (VHH) in tandem, a CD8α hinge/transmembrane region, a 4-1BB costimulatory domain, and a CD3-zeta activation domain. The bivalent VHH design improves avidity for B-cell maturation antigen (BCMA), expressed on malignant plasma cells. After lymphodepleting fludarabine + cyclophosphamide conditioning, a single IV infusion produces in vivo expansion + sustained cytotoxicity against BCMA+ myeloma cells. Approved by FDA Feb 2022 and EMA May 2022 for relapsed/refractory multiple myeloma after ≥4 prior lines (CARTITUDE-1) and expanded in 2024 to 2L+ R/R MM in lenalidomide-refractory patients (CARTITUDE-4). |
| Typical dosing | Single IV infusion, target dose 0.75 × 10⁶ CAR-positive viable T cells/kg (range 0.5-1.0 × 10⁶/kg; cap 1.0 × 10⁸ total CAR+ cells). Administered 2-5 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. No maintenance; single infusion. Bridging therapy may be used during the 4-7 week manufacturing window. In patients with CrCl 30-59 mL/min, fludarabine reduced to 24 mg/m² × 3 d; cyclophosphamide unchanged. Dose hold / delay if active infection, ANC <1,000/µL prior to lymphodepletion, or rapidly progressive extramedullary disease (con... |
| Ukraine registered | False |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-04-27 |
Warnings
- Cytokine release syndrome (CRS) — Grade ≥3 ~5% in CARTITUDE-1 (any-grade ~95%); tocilizumab + ICU support mandatory
- Immune effector cell-associated neurotoxicity syndrome (ICANS) — Grade ≥3 ~9%
- Parkinsonism and other delayed/movement neurotoxicities — distinctive cilta-cel signal (~5-6%); may be delayed weeks-months and fatal
- Guillain-Barré syndrome and cranial nerve palsies (rare but serious)
- Hemophagocytic lymphohistiocytosis / macrophage activation syndrome (HLH/MAS)
- Prolonged and recurrent cytopenias with secondary infections
- Secondary T-cell malignancies (FDA class boxed warning, 2024)
- REMS / FACT-JACIE accreditation required for administration
Notes
Pivotal: CARTITUDE-1 (Berdeja et al., Lancet 2021) — 97 heavily pretreated R/R MM patients (median 6 prior lines), ORR 97%, sCR 67%, median PFS 34.9 months (longest of any single-agent therapy in this population). FDA approval Feb 2022; CARTITUDE-4 (NEJM 2023) shifted approval to 2L+ in lenalidomide-refractory patients. Distinctive cilta-cel signal: delayed movement disorders (parkinsonism, cranial nerve palsies) — incidence ~5-6%, partly mitigated by stricter patient selection and aggressive early CRS/ICANS management. Manufacturing window 4-7 weeks. Ukraine: NOT registered, NO domestic CAR-T manufacturing. Access only via cross-border referral (EBMT/JACIE EU centers) under "Лікування за кордоном" (наказ МОЗ 988); approximate all-in cost USD 450-550K including manufacturing, lymphodepletion, ICU support, and post-CAR-T immunoglobulin replacement / infection prophylaxis. Compare to teclistamab (BCMA × CD3 bispecific) — off-the- shelf alternative with no manufacturing delay but lower depth/duration of response.
Used By
Regimens
REG-CILTACEL-MM-2L- Ciltacabtagene autoleucel (cilta-cel) BCMA CAR-T for lenalidomide-refractory R/R multiple...REG-CILTACEL-MM-3L- Ciltacabtagene autoleucel (cilta-cel) BCMA CAR-T for R/R multiple myeloma after ≥3 prior...