axicabtagene ciloleucel: clinical use

Prescribing considerations

• Restrict administration to qualified centres with trained haematology teams, immediate emergency support and access to appropriate cytokine release syndrome treatment.
• Confirm patient identity against the patient-specific bag and maintain full traceability.
• Delay infusion for unresolved serious treatment toxicity, active uncontrolled infection or active graft-versus-host disease.
• Screen for hepatitis B, hepatitis C and HIV before cell collection.
• Assess cardiac, pulmonary, renal, hepatic and neurological status.
• Consider tumour lysis risk, previous CD19-directed therapy and whether disease remains CD19-positive.
• Arrange long-term follow-up and lifelong surveillance for secondary malignancies.

Contraindications and cautions

• Hypersensitivity to axicabtagene ciloleucel, an excipient or possible residual gentamicin.
• Contraindications to the preparatory lymphodepleting chemotherapy must also be considered.
• The product must never be given to anyone other than the patient for whom it was manufactured.

Monitoring

• Monitor closely for cytokine release syndrome, neurological toxicity, hypersensitivity and organ dysfunction.
• Monitor blood counts for prolonged cytopenias and assess promptly for febrile neutropenia or infection.
• Monitor immunoglobulins and manage recurrent infections associated with B-cell aplasia or hypogammaglobulinaemia.
• Monitor for tumour lysis syndrome and viral reactivation where clinically relevant.
• Maintain lifelong surveillance for secondary malignancies, including T-cell and myeloid malignancies.

Clinical pharmacology

Autologous T cells are genetically modified with a retroviral vector to express an anti-CD19 CAR incorporating CD28 and CD3-zeta signalling domains. CD19 engagement triggers T-cell activation, expansion, cytokine secretion and killing of CD19-expressing cells.

Formulation and product differences

• Patient-specific, cryopreserved dispersion for intravenous infusion.
• Contains DMSO, sodium chloride and human albumin and may contain residual gentamicin.
• Must not be irradiated, mixed with other medicines or administered through a leukodepleting filter.