TECVAYLI Solution for injection Ref.[50315] Active ingredients: Teclistamab

Treatment with TECVAYLI should be initiated and supervised by physicians experienced in the treatment of multiple myeloma.

TECVAYLI should be administered by a healthcare professional with adequately trained medical personnel and appropriate medical equipment to manage severe reactions, including cytokine release syndrome (CRS) (see section 4.4).

Posology

Pre-treatment medicinal products should be administered prior to each dose of TECVAYLI in the step-up dosing schedule (see below).

TECVAYLI step-up dosing schedule should not be administered in patients with active infection (see Table 3 and section 4.4).

Recommended dosing schedule

The recommended dosing schedule for TECVAYLI is provided in Table 1. The recommended doses of TECVAYLI are 1.5 mg/kg by subcutaneous injection (SC) weekly, preceded by step-up doses of 0.06 mg/kg and 0.3 mg/kg.

Treatment with TECVAYLI should be initiated according to the step-up dosing schedule in Table 1 to reduce the incidence and severity of cytokine release syndrome. Due to the risk of cytokine release syndrome, patients should be instructed to remain within proximity of a healthcare facility, and monitored for signs and symptoms daily for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule (see section 4.4).

Failure to follow the recommended doses or dosing schedule for initiation of therapy, or re-initiation of therapy after dose delays, may result in increased frequency and severity of adverse reactions related to mechanism of action, particularly cytokine release syndrome (see section 4.4).

Table 1. TECVAYLI dosing schedule:

^a Dose is based on actual body weight and should be administered subcutaneously.
^b Step-up dose 2 may be given between 2 to 7 days after Step-up dose 1.
^c First maintenance dose may be given between 2 to 7 days after Step-up dose 2. This is the first full treatment dose (1.5 mg/kg).
^d Maintain a minimum of five days between weekly maintenance doses.
^e See Table 2 for recommendations on restarting TECVAYLI after dose delays.

Duration of treatment

Patients should be treated with TECVAYLI until disease progression or unacceptable toxicity.

Pre-treatment medicinal products

The following pre-treatment medicinal products must be administered 1 to 3 hours before each dose of the TECVAYLI step-up dosing schedule (see Table 1) to reduce the risk of cytokine release syndrome (see sections 4.4 and 4.8).

• Corticosteroid (oral or intravenous dexamethasone 16 mg)
• Antihistamine (oral or intravenous diphenhydramine 50 mg, or equivalent)
• Antipyretics (oral or intravenous acetaminophen 650 to 1 000 mg, or equivalent)

Administration of pre-treatment medicinal products may also be required prior to administration of subsequent doses of TECVAYLI for the following patients:

• Patients who repeat doses within the TECVAYLI step-up dosing schedule due to dose delays (Table 2), or
• Patients who experienced CRS following the previous dose (Table 3).

Prevention of herpes zoster reactivation

Prior to starting treatment with TECVAYLI, antiviral prophylaxis should be considered for the prevention of herpes zoster virus reactivation, per local institutional guidelines.

Restarting TECVAYLI after dose delay

If a dose of TECVAYLI is delayed, therapy should be restarted based on the recommendations listed in Table 2 and TECVAYLI resumed according to the dosing schedule (see Table 1). Pre-treatment medicinal products should be administered as indicated in Table 2. Patients should be monitored accordingly (see section 4.2).

Table 2. Recommendations for restarting therapy with TECVAYLI after dose delay:

^a Pre-treatment medicinal products should be administered prior to TECVAYLI dose and patients monitored accordingly.

Dose modifications

Treatment with TECVAYLI should be initiated according to the step-up dosing schedule in Table 1.

Dose reductions of TECVAYLI are not recommended.

Dose delays may be required to manage toxicities related to TECVAYLI (see section 4.4).

Recommendations on restarting TECVAYLI after a dose delay are provided in Table 2. Recommended actions after adverse reactions following administration of TECVAYLI are listed in Table 3.

Table 3. Recommended actions taken after adverse reactions following administration of TECVAYLI:

^a Based on American Society for Transplantation and Cellular Therapy (ASTCT) grading for CRS (Lee et al 2019).
^b Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as antipyretics or anticytokine therapy (e.g., tocilizumab or corticosteroids).
^c Low-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min.
^d Based on ASTCT grading for ICANS.
^e Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03.

Special populations

Paediatric population

There is no relevant use of TECVAYLI in the paediatric population for the treatment of multiple myeloma.

Elderly (65 years of age and older)

No dosage adjustment is necessary (see section 5.2).

Renal impairment

No dosage adjustment is recommended for patients with mild or moderate renal impairment (see section 5.2).

Hepatic impairment

No dosage adjustment is recommended for patients with mild hepatic impairment (see section 5.2).

Method of administration

TECVAYLI is for subcutaneous injection only.

For instructions on handling of the medicinal product before administration, see section 6.6.

Symptoms and signs

The maximum tolerated dose of teclistamab has not been determined. In clinical studies, doses of up to 6 mg/kg have been administered.

Treatment

In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be instituted immediately.

Unopened vial:

18 months.

Prepared syringe:

The prepared syringes should be administered immediately. If immediate administration is not possible, in-use storage times of the prepared syringe should be no longer than 20 hours at 2°C-8°C or ambient temperature (15°C–30°C). Discard after 20 hours if not used.

Store in a refrigerator (2°C-8°C).

Do not freeze.

Store in the original carton in order to protect from light.

3 mL solution for injection in a Type 1 glass vial with an elastomeric closure, and aluminium seal with a flip-off button containing 30 mg of teclistamab (10 mg/mL). Pack size of 1 vial.

1.7 mL solution for injection in a Type 1 glass vial with an elastomeric closure, and aluminium seal with a flip-off button containing 153 mg of teclistamab (90 mg/mL). Pack size of 1 vial.

It is very important that the instructions for preparation and administration provided in this section are strictly followed to minimise potential dosing errors with TECVAYLI 10 mg/mL and TECVAYLI 90 mg/mL vials.

TECVAYLI should be administered via subcutaneous injection only. Do not administer TECVAYLI intravenously.

TECVAYLI should be administered by a healthcare professional with adequately trained medical personnel and appropriate medical equipment to manage severe reactions, including cytokine release syndrome (see section 4.4).

TECVAYLI 10 mg/mL and TECVAYLI 90 mg/mL vials are for single use only.

TECVAYLI vials of different concentrations should not be combined to achieve maintenance dose.

Aseptic technique should be used to prepare and administer TECVAYLI.

Any unused medicinal product or waste material should be disposed in accordance with local requirements.

Preparation of TECVAYLI:

• Verify the prescribed dose for each TECVAYLI injection. To minimise errors, use the following tables to prepare TECVAYLI injection.

Use Table 9 to determine the total dose, injection volume and number of vials required, based on patient’s actual body weight for Step-up dose 1 using TECVAYLI 10 mg/mL vial.

Table 9. Injection volumes of TECVAYLI (10 mg/mL) for Step-up dose 1 (0.06 mg/kg):

Use Table 10 to determine the total dose, injection volume and number of vials required based on patient’s actual body weight for Step-up dose 2 using TECVAYLI 10 mg/mL vial.

Table 10. Injection volumes of TECVAYLI (10 mg/mL) for Step-up dose 2 (0.3 mg/kg):

Use Table 11 to determine the total dose, injection volume and number of vials required based on patient’s actual body weight for the maintenance dose using TECVAYLI 90 mg/mL vial.

Table 11. Injection volumes of TECVAYLI (90 mg/mL) for maintenance dose (1.5 mg/kg):

• Remove the appropriate TECVAYLI vial from refrigerated storage (2°C–8°C) and equilibrate to ambient temperature (15°C–30°C), as needed, for at least 15 minutes. Do not warm TECVAYLI in any other way.
• Once equilibrated, gently swirl the vial for approximately 10 seconds to mix. Do not shake.
• Withdraw the required injection volume of TECVAYLI from the vial(s) into an appropriately sized syringe using a transfer needle. o Each injection volume should not exceed 2.0 mL. Divide doses requiring greater than 2.0 mL equally into multiple syringes.
• TECVAYLI is compatible with stainless steel injection needles and polypropylene and polycarbonate syringe material.
• Replace the transfer needle with an appropriately sized needle for injection.
• Visually inspect TECVAYLI for particulate matter and discolouration prior to administration. Do not use if the solution is discoloured, or cloudy, or if foreign particles are present.
  • TECVAYLI solution for injection is colourless to light yellow.

Administration of TECVAYLI:

• Inject the required volume of TECVAYLI into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, TECVAYLI may be injected into the subcutaneous tissue at other sites (e.g., thigh). If multiple injections are required, TECVAYLI injections should be at least 2 cm apart.
• Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact.