tisagenlecleucel: clinical use

Prescribing considerations

• Initiate and administer only in a qualified centre with trained staff, emergency equipment and immediate access to measures for managing cytokine release syndrome.
• Confirm availability of the patient-specific product before preparatory treatment and verify identity against every bag and batch document before administration.
• Delay infusion for unresolved serious toxicity from previous therapy, active uncontrolled infection, active graft-versus-host disease or significant disease worsening after lymphodepletion.
• Assess previous anti-CD19 therapy, active central nervous system disease and recent stem-cell transplantation when evaluating benefit and risk.
• Do not permit subsequent donation of blood, organs, tissues or cells; maintain long-term traceability and follow-up.

Contraindications and cautions

• Hypersensitivity to tisagenlecleucel or an excipient, including dimethyl sulfoxide and dextran 40.
• Any contraindication to required lymphodepleting chemotherapy must also be considered.
• Never administer the product to anyone other than the patient from whom the cells were collected.

Monitoring

• Before cell collection and treatment: assess infection; screen for HBV, HCV and HIV; test for pregnancy where relevant; and evaluate cardiovascular, respiratory and neurological status.
• After infusion: monitor for cytokine release syndrome, ICANS and other neurological events, infection, febrile neutropenia, cytopenias, tumour lysis syndrome and organ dysfunction.
• Monitor blood counts and immunoglobulin levels; consider infection prophylaxis and immunoglobulin replacement according to clinical findings and local practice.
• Maintain lifelong surveillance for secondary malignancy, including malignancies of T-cell origin.

Clinical pharmacology

Autologous T cells are transduced ex vivo with a lentiviral vector encoding an anti-CD19 CAR containing CD3-zeta signalling and a 4-1BB co-stimulatory domain. CD19 binding activates antitumour activity and supports expansion and persistence of the modified cells.

Formulation and product differences

• Patient-specific, colourless to slightly yellow dispersion for intravenous infusion supplied frozen in one or more bags.
• Cell concentration, cellular composition, bag volume and number of bags vary between patient batches and are documented on batch-specific paperwork.
• Contains human albumin, dimethyl sulfoxide and dextran 40; serious hypersensitivity reactions have been reported.
• Must remain frozen under cryogenic conditions until required, must not be refrozen after thawing and must not be mixed with other medicinal products.