Inbrija
Inbrija
Generic Name
Inbrija
Mechanism
Inbrija is a autologous chimeric antigen receptor T (CAR‑T) cell therapy that targets the *CD19* antigen expressed on B‑cell leukemias and lymphomas.
Key points
• The patient's own T cells are transduced with a lentiviral vector encoding a CD19‑specific single‑chain variable fragment (scFv).
• The CAR construct includes:
• An extracellular scFv that binds CD19.
• A hinge and transmembrane domain.
• An intracellular CD3ε signaling domain.
• A CD28 costimulatory domain that enhances activation, proliferation, and persistence.
• Once infused, CAR‑T cells recognize and kill CD19‑positive malignant B cells, leading to rapid tumor lysis and potential long‑term remission.
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Pharmacokinetics
- Cell Expansion & Persistence: In vivo proliferation follows a sigmoid curve; peak expansion occurs 5–14 days post‑infusion.
- Distribution: CAR‑T cells circulate in blood and infiltrate lymphoid organs, bone marrow, and, rarely, the CNS.
- Half‑life: Variable; CAR‑T cells may persist for weeks to months, with a median persistence of ~4 months in responders.
- Metabolism/Excretion: N/A – as living cells, excretion is via apoptosis, senescence, or clearance by macrophages.
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Indications
Inbrija is indicated for adults (≥18 years) with:
• Relapsed or refractory *large B‑cell lymphoma* (LBCL) after ≥2 prior lines of systemic therapy, including diffuse large B‑cell lymphoma (DLBCL), high‑grade B‑cell lymphoma (HGBL), and primary mediastinal B‑cell lymphoma (PMBCL).
• Prior exposure to rituximab and an anthracycline‑containing regimen.
• Lymphoma with measurable disease and ECOG performance status 0‑2.
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Contraindications
| Category | Details |
| Contraindications | None listed, but use is discouraged in: • Active, uncontrolled infection • Ongoing uncontrolled CNS disease or intracranial bleeds |
| Warnings |
• Cytokine Release Syndrome (CRS) – risk factors: high tumor burden, high CAR‑T cell dose. • Immune Effector Cell‑Associated Neurotoxicity Syndrome (ICANS). • Infections – immunosuppressed post‑infusion. • Tumor Lysis Syndrome (TLS). • Allergic reactions to viral vectors. |
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Dosing
- Dose: 125 000 CAR‑T cells/kg (total cells per infusion).
- Conditioning Regimen: Lymphodepleting chemotherapy – *fludarabine 30 mg/m²* + *cyclophosphamide 500 mg/m²* on days −5, −4, −3, and −2.
- Infusion: Single IV infusion over 1–2 hours on Day 0.
- Supportive Medications:
- Pre‑infusion: IV dexamethasone 12 mg (for cytokine prophylaxis).
- Post‑infusion: Tocilizumab 8 mg/kg and/or anakinra 100 mg subcutaneously for CRS as needed.
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Adverse Effects
| Common (≥30 %) | Serious (≥5 %) |
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• Fever • Chills • Nausea • Fatigue • Headache • Bone marrow suppression (neutropenia, thrombocytopenia) |
• Cytokine Release Syndrome (grade 3‑4) • ICANS (grade 3‑4) • Severe infections (bacterial, viral, fungal) • Tumor Lysis Syndrome • Hypofibrinogenemia • Cardiovascular toxicity (hypotension, arrhythmias) |
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Monitoring
- Baseline: CBC, CMP, LDH, uric acid, IL‑6, bilirubin, coagulation panel, imaging (CT/PET), neurological baseline.
- Post‑infusion (Days 0‑28):
- Daily CBC and CMP for first 7 days; then every 3–5 days until recovery.
- Daily VAS for fever, blood pressure, oxygen saturation.
- Neurological exam twice daily.
- IL‑6 and ferritin levels if CRS suspected.
- Imaging at Day 28 and at 3, 6, 12 months to assess response.
- Long‑term: Monitor for B‑cell aplasia (CD19⁺ B cells) and immunoglobulin levels; screen for infections prophylactically.
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Clinical Pearls
- Early CRS Identification: Use the CAR‑T‑specific *EASIX* score; pre‑emptive tocilizumab for patients with high IL‑6 (>150 pg/mL) or rapid fevers (>38.5 °C).
- ICANS Management: Initiate high‑dose steroids (solumedrol 15 mg/kg/d) immediately; consider neurology consult if grade ≥2.
- Cell Storage: Keep the product refrigerated (2–8 °C) until administration; thawed cells should be used within 4–6 hours.
- Patient Selection: Lower tumor burden (3 months to prevent hypogammaglobulinemia‑related infections.
- Documentation: Record exact time of infusion start/stop; precise cell count; any adverse event grading per *Common Terminology Criteria for Adverse Events (CTCAE)*.
- Education: Instruct patients to report sudden neurological changes, seizures, or severe headache within 24 h, as early neurotoxicity can worsen rapidly.
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