CARVYKTI Dispersion for infusion Ref.[50034] Active ingredients: Ciltacabtagene autoleucel

CARVYKTI must be administered in a qualified treatment centre. Therapy should be initiated under the direction and supervision of a healthcare professional experienced in the treatment of haematological malignancies and trained for administration and management of patients treated with CARVYKTI. Prior to infusion, the qualified treatment centre must have at least 1 dose of tocilizumab available for use in the event of cytokine release syndrome (CRS), with access to an additional dose within 8 hours of each previous dose (see section 4.4). In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion. Emergency equipment must be available prior to infusion and during the recovery period.

Posology

CARVYKTI is intended for autologous use (see section 4.4).

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

The target dose is 0.75 × 10⁶ CAR-positive viable T cells/kg of body weight (not exceeding 1.0 × 10⁸ CAR-positive viable T cells).

Patients 100 kg and below: 0.5 – 1.0 × 10⁶ CAR-positive viable T cells/kg body weight.

Patients above 100 kg: 0.5 – 1.0 × 10⁸ CAR-positive viable T cells (non-weight based).

See the accompanying Lot information sheet (LIS) for additional information pertaining to dose.

Bridging therapy

Consider bridging therapy according to prescriber’s choice prior to infusion with CARVYKTI to reduce tumour burden or stabilise the disease (see section 4.4).

Pre-treatment (lymphodepleting regimen)

Lymphodepleting regimen must be delayed if a patient has serious adverse reactions from preceding bridging therapies (including clinically significant active infection, cardiac toxicity, and pulmonary toxicity) (see section 5.1).

The availability of CARVYKTI should be confirmed prior to starting the lymphodepleting regimen. A lymphodepleting regimen of cyclophosphamide 300 mg/m² intravenous and fludarabine 30 mg/m² intravenous should be administered daily for 3 days. CARVYKTI infusion should be administered 5 to 7 days after the start of the lymphodepleting regimen. If resolution of toxicities due to the lymphodepleting regimen to Grade 1 or lower takes more than 14 days, thereby resulting in delays to CARVYKTI dosing, the lymphodepleting regimen should be re-administered after a minimum of 21 days following the first dose of the first lymphodepleting regimen.

For dose modifications of cyclophosphamide and fludarabine, see corresponding Summaries of Product Characteristics of cyclophosphamide and fludarabine.

Premedication

The following pre-infusion medications should be administered to all patients 30 to 60 minutes prior to CARVYKTI infusion:

• Antipyretic (oral or intravenous paracetamol 650 to 1,000 mg).
• Antihistamine (oral or intravenous diphenhydramine 25 to 50 mg or equivalent).

The use of prophylactic systemic corticosteroids should be avoided as it may interfere with the activity of CARVYKTI.

Special populations

Elderly

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

Patients seropositive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)

There is currently no experience with manufacturing CARVYKTI for patients testing positive for HIV, active HBV, or active HCV. Screening for HBV, HCV and HIV and other infectious agents must be performed before collection of cells for manufacturing.

Paediatric population

The safety and efficacy of CARVYKTI in children aged below 18 years of age have not been established.

No data are available.

Method of administration

CARVYKTI is for intravenous use only.

Do NOT use a leukodepleting filter.

Preparation of CARVYKTI for infusion

Prior to infusion and during the recovery period, the availability of tocilizumab, or suitable alternatives, in the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, and emergency equipment must be ensured.

Before infusion, it must be confirmed that the patient’s identity matches the unique patient information on the CARVYKTI cryo cassette, infusion bag and on the Lot Information Sheet. (see section 4.4).

The medicinal product must not be thawed until it is ready to be used. The timing of CARVYKTI thaw and infusion should be coordinated; the infusion time should be confirmed in advance, and the start time for thaw must be adjusted so that CARVYKTI is available for infusion when the patient is ready. The medicinal product should be administered immediately after thawing and the infusion should be completed within 2.5 hours of thawing.

For detailed instructions on preparation, administration, measures to take in case of accidental exposure and disposal of CARVYKTI, see section 6.6.

There are no data regarding the signs or sequelae of overdose with CARVYKTI.

9 months.

Once thawed: maximum 2.5 hours at room temperature (20°C to 25°C). CARVYKTI infusion must be administered immediately after thawing and completed within 2.5 hours.

CARVYKTI must be stored and transported in the vapour phase of liquid nitrogen (≤ -120°C) and must remain frozen until the patient is ready for treatment to ensure viable cells are available for patient administration.

Thawed medicinal product must not be shaken, refrozen or refrigerated.

Keep infusion bag in the aluminum cryo cassette.

For storage conditions after thawing of the medicinal product, see section 6.3.

Ethylene vinyl acetate (EVA) infusion bag with sealed addition tube and two available spike ports containing either 30 mL (50 mL bag) or 70 mL (250 mL bag) of cell dispersion. Each infusion bag is packed in an aluminium cryo cassette.

CARVYKTI should not be irradiated as irradiation could inactivate the medicinal product.

Precautions to be taken before handling or administering the medicinal product

CARVYKTI should be transported within the facility in closed, break-proof and leak-proof containers.

This medicinal product contains human blood cells. Healthcare professionals handling CARVYKTI should take appropriate precautions (wearing gloves, protective clothing and eye protection) to avoid potential transmission of infectious diseases. CARVYKTI must remain ≤ -120 °C at all times, until the content of the bag is thawed for infusion.

Preparation prior to administration

The timing of CARVYKTI thaw and infusion should be coordinated; the infusion time should be confirmed in advance, and the start time for thaw must be adjusted so that CARVYKTI is available for infusion when the patient is ready. Once thawed, the medicinal product should be administered immediately and the infusion should be completed within 2.5 hours.

• Prior to CARVYKTI preparation, patient identity should be confirmed by matching the patient’s identity with the patient identifiers on the CARVYKTI cryo cassette and Lot Information Sheet. The CARVYKTI infusion bag should not be removed from the cryo cassette if the information on the patient-specific label does not match the intended patient.
• Once patient identification is confirmed, the CARVYKTI infusion bag should be removed from the cryo cassette.
• The infusion bag should be inspected for any breaches of container integrity such as breaks or cracks before thawing. Do not administer if the bag is compromised and contact Janssen-Cilag International NV.

Thawing:

• The infusion bag should be placed inside a sealable plastic bag prior to thawing.
• CARVYKTI should be thawed at 37°C±2°C using either a water bath or dry thaw device until there is no visible ice in the infusion bag. Total time from start of thaw until completion of thawing should be no more than 15 minutes.
• The infusion bag should be removed from the sealable plastic bag and wiped dry. The contents of the infusion bag should be gently mixed to disperse clumps of cellular material. If visible cell clumps remain, the contents of the bag should continue to be gently mixed. Small clumps of cellular material should disperse with gentle manual mixing. CARVYKTI must not be pre-filtered into a different container, washed, spun down, and/or resuspended in new media prior to infusion.
• Once thawed, the medicinal product should not be re-frozen or refrigerated.

Administration:

• CARVYKTI is for autologous single use only.
• Prior to infusion and during the recovery period, ensure tocilizumab and emergency equipment are available for use.
• Confirm the patient’s identity with the patient identifiers on the CARVYKTI infusion bag and Lot Information Sheet. Do not infuse CARVYKTI if the information on the patient-specific label does not match the intended patient.
• Once thawed, the entire contents of the CARVYKTI bag should be administered by intravenous infusion within 2.5 hours at room temperature (20 °C to 25 °C), using infusion sets fitted with an in-line filter. The infusion usually takes less than 60 minutes.
• Do NOT use a leukodepleting filter.
• Gently mix the contents of the bag during CARVYKTI infusion to disperse cell clumps.
• After the entire content of the product bag is infused, flush the administration line, inclusive of the in-line filter, with sodium chloride 9 mg/mL (0.9%) solution for injection to ensure all medicinal product is delivered.

Precautions to be taken for the disposal of the medicinal product

Unused medicinal product and all material that has been in contact with CARVYKTI (solid and liquid waste) should be handled and disposed of as potentially infectious waste in accordance with local guidelines on handling of human-derived material.

Measures to take in case of accidental exposure

In case of accidental exposure local guidelines on handling of human-derived material should be followed. Work surfaces and materials which have potentially been in contact with CARVYKTI must be decontaminated with appropriate disinfectant.