BLENREP Powder for concentrate for solution for infusion Ref.[50842] Active ingredients: Belantamab mafodotin

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

Recommended supportive care

Patients should have an ophthalmic examination (including visual acuity and slit lamp examination) performed by an eye care professional at baseline, before the subsequent 3 treatment cycles, and as clinically indicated whilst on treatment (see section 4.4).

Physicians should advise patients to administer preservative-free artificial tears at least 4 times a day beginning on the first day of infusion and continuing until completion of treatment as this may reduce corneal symptoms (see section 4.4).

For patients with dry eye symptoms, additional therapies may be considered as recommended by their eye care professional.

Posology

The recommended dose is 2.5 mg/kg of BLENREP administered as an intravenous infusion once every 3 weeks.

It is recommended that treatment should be continued until disease progression or unacceptable toxicity (see section 4.4).

Dose modifications

Recommended dose modifications for corneal adverse reactions are provided in Table 1. Table 2 provides dose modifications recommended for other adverse reactions.

Management of corneal adverse reactions

Corneal adverse reactions may include findings upon eye examination and/or changes in visual acuity (see sections 4.4 and 4.8). The treating physician should review the patient’s ophthalmic examination report before dosing and should determine the dose of BLENREP based on the highest category from the report in the most severely affected eye as both eyes may not be affected to the same degree (Table 1).

During the ophthalmic examination, the eye care professional should assess the following:

• The corneal examination finding(s) and the decline in best corrected visual acuity (BCVA).
• If there is a decline in BCVA, the relationship of corneal examination findings to BLENREP should be determined.
• The highest category grading for these examination findings and BCVA should be reported to the treating physician.

Table 1. Dose modifications for corneal adverse reactions:

^a The severity category is defined by the most severely affected eye as both eyes may not be affected to the same degree.
^b Mild superficial keratopathy (documented worsening from baseline), with or without symptoms.
^c Moderate superficial keratopathy – with or without patchy microcyst-like deposits, sub-epithelial haze (peripheral), or a new peripheral stromal opacity.
^d Severe superficial keratopathy with or without diffuse microcyst-like deposits involving the central cornea, sub-epithelial haze (central), or a new central stromal opacity.
^e A corneal defect may lead to corneal ulcers. These should be managed promptly and as clinically indicated by an eye care professional.

Table 2. Dose modifications for other adverse reactions:

Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).

Special populations

Elderly

No dose adjustment is required for elderly patients (see section 5.2).

Renal impairment

No dose adjustment is required in patients with mild or moderate renal impairment (eGFR 30 mL/min). There are insufficient data in patients with severe renal impairment to support a dose recommendation (see section 5.2).

Hepatic impairment

No dose adjustment is required in patients with mild hepatic impairment (bilirubin greater than ULN to less than or equal to 1.5 × ULN or aspartate transaminase [AST] greater than ULN). There are insufficient data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment to support a dose recommendation (see section 5.2).

Body weight

BLENREP has not been studied in patients with body weight <40 kg or >130 kg (see section 5.2).

Paediatric population

The safety and efficacy of BLENREP in children and adolescents below 18 years of age have not been established. No data are available.

Method of administration

BLENREP is for intravenous use.

BLENREP must be reconstituted and diluted by a healthcare professional prior to administration as an intravenous infusion. BLENREP should be infused over a minimum of 30 minutes (see section 6.6).

There has been no experience of overdosage in clinical studies.

There is no known specific antidote for belantamab mafodotin overdose. In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse effects and appropriate supportive treatment should be instituted immediately.

Unopened vial:

3 years.

Reconstituted solution:

The reconstituted solution can be stored for up to 4 hours at room temperature (20ºC to 25ºC) or stored in a refrigerator (2°C to 8°C) for up to 4 hours. Do not freeze.

Diluted solution:

From a microbiological point of view, the product should be used immediately. If not used immediately, the diluted solution can be stored in a refrigerator (2ºC to 8ºC) prior to administration for up to 24 hours. Do not freeze. If refrigerated, allow the diluted solution to equilibrate to room temperature prior to administration.

The diluted infusion solution may be kept at room temperature (20ºC to 25ºC) for a maximum of 6 hours (including infusion time).

Store in a refrigerator (2ºC to 8ºC).

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

Type 1 glass vial sealed with bromobutyl rubber stopper and aluminium overseal with a plastic removable cap containing 100 mg powder.

Pack size: 1 vial.

Preparation of solution for infusion:

BLENREP is a cytotoxic anticancer medicinal product. Proper handling procedures should be followed. Use aseptic technique for the reconstitution and dilution of the dosing solution.

The recommended dose of BLENREP is 2.5 mg/kg administered as an intravenous infusion once every 3 weeks.

Calculate the dose (mg), total volume (mL) of solution required and the number of vials needed based on the patient’s actual body weight (kg).

Reconstitution:

1. Remove the vial(s) of BLENREP from the refrigerator and allow to stand for approximately 10 minutes to reach room temperature.
2. Reconstitute each vial with 2 mL of water for injections to obtain a concentration of 50 mg/mL. Gently swirl the vial to aid dissolution. Do not shake.
3. Visually inspect the reconstituted solution for particulate matter and discoloration. The reconstituted solution should be a clear to opalescent, colourless to yellow to brown liquid. Discard the reconstituted vial if extraneous particulate matter other than translucent to white proteinaceous particles is observed.

Dilution Instructions for Intravenous Use:

1. Withdraw the necessary volume for the calculated dose from each vial.
2. Add the necessary amount of BLENREP to the infusion bag containing 250 mL of sodium chloride 9 mg/mL (0.9%) solution for injection. Mix the diluted solution by gentle inversion. The final concentration of the diluted solution should be between 0.2 mg/mL to 2 mg/mL. DO NOT SHAKE.
3. Discard any unused reconstituted solution of BLENREP left in the vial.

If the diluted solution is not used immediately, it may be stored in a refrigerator (2ºC to 8ºC) for up to 24 hours prior to administration. If refrigerated, allow the diluted solution to equilibrate to room temperature prior to administration. The diluted solution may be kept at room temperature (20ºC to 25ºC) for a maximum of 6 hours (including infusion time).

Administration Instructions:

1. Administer the diluted solution by intravenous infusion over a minimum of 30 minutes using an infusion set made of polyvinyl chloride or polyolefin.
2. Filtration of the diluted solution is not required. However, if the diluted solution is filtered, polyethersulfone (PES) based filter is recommended.

Disposal:

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