Generic Name

Tecartus

Mechanism

• Tecartus (*tisagenlecleucel*) is a chimeric antigen receptor T‑cell (CAR‑T) therapy that targets the CD19 surface antigen expressed on B‑cell malignancies.
• The patient’s own CD3⁺ T cells are collected, genetically engineered ex‑vivo with a lentiviral vector encoding a CD19‑specific single‑chain variable fragment (scFv) linked to intracellular signaling domains (CD3ζ and a co‑stimulatory domain such as CD28 or 4-1BB).
• After expansion, the autologous CAR‑T cells are infused intravenously. They recognize and bind CD19 on malignant B cells, become activated, proliferate, and mediate cytotoxic killing via perforin/granzyme release, cytokine production, and induction of apoptosis.
• The CAR‑T cells persist for months to years, providing ongoing surveillance and rapid killing of any residual disease.

Pharmacokinetics

• Absorption: Not applicable (cellular product).
• Distribution: Systemic distribution with widespread trafficking to lymphoid tissues and marrow.
• Metabolism: Cellular proliferation and activity; no classic metabolic pathways.
• Elimination: CAR‑T cell lifespan varies; most decline after initial expansion, but a small population can persist long‑term.
• Half‑life: Peak expansion typically occurs 5–14 days post‑infusion; the overall presence of CAR‑T cells can be detected for many months, sometimes years, depending on disease control.
• Interactions: No known drug–drug interactions; however, concomitant immunosuppression (e.g., steroids) can blunt efficacy.

Indications

• Relapsed or refractory B‑cell precursor acute lymphoblastic leukemia (ALL) in patients 12 months or older when at least 3 prior lines of therapy have failed.
• Relapsed or refractory B‑cell non‑Hodgkin lymphoma (B‑cell NHL) after at least 2 prior lines of therapy, which includes immunochemotherapy and an anti‑CD20 monoclonal antibody.

Contraindications

• Contraindications:
• Active, uncontrolled infection (bacterial, viral, fungal, or parasitic) at the time of leukapheresis or infusion.
• Prior CAR‑T therapy targeting CD19 (risk of re‑infusion toxicities).
• Warnings:
• Cytokine Release Syndrome (CRS): incidence ~90%; can progress to hypoxia, hypotension, shock.
• Immune‑Mediated Encephalopathy Syndrome (ICANS): neurotoxicity involving confusion, seizures, aphasia.
• B‑cell aplasia and hypogammaglobulinemia, leading to increased infection risk.
• Tumor Lysis Syndrome (TLS) in patients with high tumor burden.
• Monitor for liver dysfunction, coagulopathy and hemorrhagic events.

Dosing

• Dose: 2 × 10⁶ CAR⁺ T cells per kilogram body weight (fixed dose of 1.0 × 10⁶ CAR⁺ cells/kg nominally).
• Preparation:
• Leukapheresis to harvest CD3⁺ T cells.
• Ex‑vivo manufacturing (≈ 2–3 weeks).
• Quality control (phenotype, potency, sterility).
• Peripheral Venous or Central Line is mandatory.
• Infusion rate:
• Initiate infusion over 4 hours; if sedation or steroids needed, adjust accordingly.
• Monitor vitals continuously; pause or stop infusion if severe CRS or neurotoxicity develops.
• Pretreatment: No mandatory pre‑medication, but patients may receive dexamethasone prophylaxis to reduce CRS severity per institutional protocol.
• Post‑infusion:
• Observation in high‑care setting (ICU/ward) for 7–14 days.
• Hospitalization may continue until CRS/ICANS resolution and platelet count >50 × 10⁹/L.

Adverse Effects

> High‑Yield Summary:

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• CRS often begins within 1–2 days; early grading (R).

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• Neurotoxicity peaks around days 4–7.

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• Close monitoring of cytokines (IL‑6, ferritin) aids early detection.

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• Steroids (dexamethasone or hydrocortisone) and tocilizumab are first‑line CRS/ICANS therapies.

Monitoring

Clinical Pearls

1. Infusion Scheduling:
• Administer Tecartus days 16–22 after prior chemotherapy to allow adequate neutrophil recovery; schedule earlier for aggressive disease if counts permit.

2. CRS Grading & Management Algorithm:
• Use Lee et al. 2014 CRS grading; for grade ≥ 2, initiate tocilizumab (8 mg/kg IV, max 800 mg).
• Persisting fever or hypotension beyond 12 h → add dexamethasone 10 mg IV/PO or hydrocortisone 100 mg IV q6h.

3. Neurotoxicity Vigilance:
• Screen for baseline neurocognitive deficits; consider prophylactic dexamethasone in patients with high tumor burden.
• Prompt neurology consult and EEG if any neuro signs; manage with steroids and, if refractory, consider anakinra.

4. Infection Prophylaxis:
• IVIG (400 mg/kg every 3–4 weeks) until IgG > 700 mg/dL and B‑cell recovery.
• Antimicrobial coverage: TMP‑SMX (quadruple strength) for 14–21 days; adjust based on cultures.

5. Manufacturing Turnaround & Shipping:
• Aim for ≤ 10 days from leukapheresis to infusion; coordinate with GMP facility in advance.
• Use temperature‑controlled shipping; ensure no treatment delays to avoid tumor progression.

6. Patient Selection & Counseling:
• Discuss risks of crushing hemolysis and secondary malignancies; shared decision‑making is critical.
• Emphasize the need for in‑hospital monitoring for at least 14 days; out‑home follow‑up may be feasible after stable.

7. Data Capture & Reporting:
• Record all CRS/ICANS events in the Safety Data Links (SDLs) from the manufacturer; contributes to real‑world safety data.

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• *This drug card provides a concise, evidence‑based overview of Tecartus tailored for medical students, residents, and practicing clinicians seeking quick reference during patient care or study. For detailed dosing schedules, handling instructions, and complete labeling, consult the FDA prescribing information and institutional protocols.*