Relapsed or refractory diffuse large B-cell lymphoma

Tisagenlecleucel is intended for autologous use only.

Treatment consists of a single dose for infusion containing a dispersion for infusion of CAR-positive viable T cells in one or more infusion bags.

Dose in adult DLBCL:

• The dose is within a range of 0.6 to 6 × 10⁸ CAR-positive viable T cells (non-weight based).

Pre-treatment conditioning (lymphodepleting chemotherapy)

The availability of tisagenlecleucel must be confirmed prior to starting the lymphodepleting regimen. Tisagenlecleucel is recommended to be infused 2 to 14 days after completion of the lymphodepleting chemotherapy.

Lymphodepleting chemotherapy may be omitted if a patient is experiencing significant cytopenia, e.g., white blood cell (WBC) count ≤1 000 cells/μL within one week prior to infusion.

If there is a delay of more than 4 weeks between completing lymphodepleting chemotherapy and the infusion and the WBC count is >1 000 cells/μL, then the patient should be re-treated with lymphodepleting chemotherapy prior to receiving tisagenlecleucel.

The recommended lymphodepleting chemotherapy regimen is:

• Fludarabine (25 mg/m² intravenous daily for 3 days) and cyclophosphamide (250 mg/m² intravenous daily for 3 days starting with the first dose of fludarabine).

If the patient experienced a previous Grade 4 haemorrhagic cystitis with cyclophosphamide, or demonstrated a chemorefractory state to a cyclophosphamide-containing regimen administered shortly before lymphodepleting chemotherapy, then the following should be used:

• Bendamustine (90 mg/m² intravenous daily for 2 days).

Pre-medication

To minimise potential acute infusion reactions, it is recommended that patients be premedicated with paracetamol and diphenhydramine or another H1 antihistamine within approximately 30 to 60 minutes prior to tisagenlecleucel infusion. Corticosteroids should not be used at any time except in the case of a lifethreatening emergency.

Clinical assessment prior to infusion

Tisagenlecleucel treatment should be delayed in some patient groups at risk.

Monitoring after infusion

• Patients should be monitored daily for the first 10 days following infusion for signs and symptoms of potential cytokine release syndrome, neurological events and other toxicities. Physicians should consider hospitalisation for the first 10 days post infusion or at the first signs/symptoms of cytokine release syndrome and/or neurological events.
• After the first 10 days following the infusion, the patient should be monitored at the physician’s discretion.
• Patients should be instructed to remain within proximity (within 2 hours of travel) of a qualified clinical facility for at least 4 weeks following infusion.

Elderly

No dose adjustment is required in patients over 65 years of age.