Lynozyfic

Patient Information Leaflet

LYNOZYFIC 5 mg concentrate for solution for infusion, 200 mg concentrate for solution for infusion

linvoseltamab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before you are given this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

1. What LYNOZYFIC is and what it is used for
2. What you need to know before you are given LYNOZYFIC
3. How LYNOZYFIC is administered
4. Possible side effects
5. How to store LYNOZYFIC
6. Contents of the pack and other information

1. What LYNOZYFIC is and what it is used for

LYNOZYFIC is an antitumor medicinal product containing the active substance linvoseltamab.
Linvoseltamab is used in adults to treat a type of bone marrow cancer called
multiple myeloma. Linvoseltamab is used as monotherapy in patients who have received at least three
prior therapies for the cancer, including an immunomodulatory agent, a proteasome inhibitor,
and an anti-CD38 antibody, and whose cancer has progressed after the most recent treatment.
The active substance in LYNOZYFIC, linvoseltamab, is a bispecific monoclonal antibody. It is a
type of protein designed to recognize and bind to two specific targets in the body: B-cell maturation antigen (BCMA) on the surface of multiple myeloma tumor cells and
CD3 on the surface of T lymphocytes (immune system cells). By binding to these target proteins,
linvoseltamab brings together tumor cells and T lymphocytes. This activates the T lymphocytes, enabling them
to eliminate multiple myeloma tumor cells.

2. What you need to know before you are given LYNOZYFIC

Do not be given LYNOZYFIC if:

• you are allergic to linvoseltamab or to any of the other ingredients of this medicine (listed in section 6).

If you are unsure whether you are allergic, consult your doctor or nurse before you are given LYNOZYFIC.
Warnings and precautions
Talk to your doctor or nurse before you are given LYNOZYFIC if:

• you have had a seizure in the past 12 months, as LYNOZYFIC may cause neurological side effects.

Tests and monitoring
Before you are given LYNOZYFIC:

• Your doctor will perform blood tests to check for signs of infection. If you have an infection, it will be treated before you start treatment with LYNOZYFIC.
• Your doctor will also check whether you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding” in section 2).

During treatment with LYNOZYFIC,
your doctor will monitor you for the development of any side effects. Your doctor will regularly check your blood cell counts, as the number of blood cells and other blood components may decrease.
Be alert to serious side effects

• Treatment with LYNOZYFIC can cause cytokine release syndrome (CRS). Cytokine release syndrome is a severe or potentially life-threatening immune reaction. Seek immediate medical help if you develop symptoms of CRS, including: fever, chills, difficulty breathing, rapid heartbeat, dizziness or feeling lightheaded.
• Treatment with LYNOZYFIC can cause a serious immune reaction called immune effector cell-associated neurotoxicity syndrome (ICANS). Contact your doctor immediately if you develop symptoms of ICANS, including: difficulty speaking, writing or understanding things, feeling confused or less alert or aware, feeling disoriented, or seizures.

Due to the possibility of developing ICANS with LYNOZYFIC, you must not drive or operate heavy machinery for 24 hours after receiving the first and second dose of LYNOZYFIC, or if during treatment with LYNOZYFIC you experience symptoms such as tiredness, dizziness or confusion.

• Treatment with LYNOZYFIC can cause serious, potentially life-threatening or fatal infections, including a rare but serious brain infection called progressive multifocal leukoencephalopathy (PML). Contact your doctor immediately if you develop symptoms of infection, including: fever, chills, shaking, fatigue, cough, shortness of breath, rapid breathing, rapid heartbeat, clumsiness, weakness, difficulty walking, changes in vision, memory loss, or difficulty speaking or thinking.
• Treatment with LYNOZYFIC can cause hypogammaglobulinemia, a condition in which the body does not produce enough immunoglobulins (also known as antibodies), which are important for fighting infections.
• Treatment with LYNOZYFIC can cause neutropenia (low levels of neutrophils, a type of white blood cell), which may increase the risk of infection and febrile neutropenia (low levels of neutrophils with fever).

Inform your doctor or nurse immediately if, during treatment with LYNOZYFIC, you experience any of the side effects listed above – see section 4 “Serious side effects” for more information. You will also be given a Patient Alert Card containing information about the side effects of CRS and ICANS that may occur with LYNOZYFIC and how to recognize them. You must carry your Patient Alert Card with you at all times and show it to any healthcare professional treating you.
Children and adolescents
Do not give LYNOZYFIC to children or adolescents under 18 years of age. This is because LYNOZYFIC has not been studied in this age group.
Other medicines and LYNOZYFIC
Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines. This includes over-the-counter medicines and herbal remedies.
Talk to your doctor or nurse before you are given LYNOZYFIC if you have recently received a vaccination or are due to receive one.
You may only receive live vaccines more than four weeks before the first dose of LYNOZYFIC or months after stopping treatment with LYNOZYFIC. Your doctor will check whether you can receive a live vaccine after stopping treatment.
Pregnancy and breastfeeding
It is not known whether LYNOZYFIC affects the unborn baby or passes into breast milk. Inform your doctor or nurse before you are given LYNOZYFIC if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. Your doctor may also perform a pregnancy test before you are given LYNOZYFIC.
Contraception
If you can become pregnant, you must use an effective method of contraception during treatment and for at least 5 months after stopping treatment with LYNOZYFIC.
Pregnancy
LYNOZYFIC is not recommended during pregnancy and in women who could become pregnant and are not using contraception. This medicine may harm the unborn baby if used during pregnancy. If you become pregnant while being treated with this medicine, inform your doctor or nurse immediately.
Breastfeeding
You must not breastfeed during treatment and for at least 5 months after your last dose of LYNOZYFIC. This is because it is not known whether LYNOZYFIC passes into breast milk and may affect the baby.
Driving and using machines
LYNOZYFIC significantly impairs the ability to drive and use machines. Do not drive, use tools or heavy machinery, or do anything that could put you at risk:

• for 24 hours after receiving the first and second dose of LYNOZYFIC, or
• if you develop new symptoms such as dizziness or confusion at any time during treatment with LYNOZYFIC (see “Possible side effects” in section 2), or
• if your doctor has advised you not to.

LYNOZYFIC contains polysorbate 80
The 5 mg vial of linvoseltamab contains 2.5 mg of polysorbate 80 in each 2.5 ml vial, equivalent to 1 mg/ml.
The 200 mg vial of linvoseltamab contains 10 mg of polysorbate 80 in each 10 ml vial, equivalent to 1 mg/ml.
Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How LYNOZYFIC is administered

LYNOZYFIC will be administered to you under the supervision of a physician experienced in the treatment of multiple myeloma. Follow the treatment schedule explained to you by your doctor. If you have any doubts, consult your doctor.

When LYNOZYFIC is administered
This medicine is initially given at lower doses, known as incremental doses, before you receive full treatment doses:

• In Week 1 Day 1, you will receive the first incremental dose of 5 mg
• In Week 2 Day 1, you will receive the second incremental dose of 25 mg
• In Week 3 Day 1, you will receive the first full treatment dose of 200 mg

You will then receive full treatment doses of 200 mg:

• Once weekly for 10 doses (from Week 4 to Week 13)
• Then every other week (from Week 14 to Week 24)

If you continue to benefit from LYNOZYFIC after at least 17 treatment doses, your doctor will decide whether you should continue receiving full treatment doses:

• Every 2 weeks, or
• Every 4 weeks (if your response to treatment is very good)

Your doctor may continue your treatment for as long as you continue to respond to LYNOZYFIC, or until side effects become too severe. Your doctor may adjust your dose or the way you receive LYNOZYFIC if you experience certain side effects.

Administration and monitoring of LYNOZYFIC
LYNOZYFIC is administered intravenously as an intravenous infusion. Your doctor will adjust the infusion time based on how you respond to treatment.

• The first incremental dose, second incremental dose, and the first full treatment dose will each be administered over 4 hours.
• You must be monitored for potential side effects during administration and for 24 hours after the first infusion.
  o This is to monitor for any signs or symptoms of CRS, infusion-related reactions (IRR), or ICANS (see section “Watch for serious side effects” in section 2).
• If you experienced CRS, ICANS, or any other moderate or severe side effect after the first dose, you must be monitored for 24 hours after the second dose.
• You should plan to remain near the location where you received treatment with a caregiver (a person who can assist you) during the 24-hour monitoring period.
• If you do not experience any side effects after the incremental doses and the first full treatment dose, your doctor may administer the next infusion over 1 hour. If this is well tolerated, your doctor may then administer subsequent infusions over 30 minutes.

Other medicines administered before treatment with LYNOZYFIC
You will be given other medications before each of the first four doses of LYNOZYFIC. These help reduce the risk of side effects such as cytokine release syndrome or infusion-related reactions. These may include medications to reduce the risk of:

• Allergic reactions (antihistamines)
• Inflammation (corticosteroids)
• Fever (such as paracetamol)

You may also receive these medications for subsequent doses of LYNOZYFIC, depending on any side effects you may experience.
Additionally, you are likely to receive other medications to reduce the risk of developing an infection and/or based on any side effects you experience or your medical history.

If you are given more LYNOZYFIC than you should
This medicine will be administered by your doctor or nurse, and it is unlikely that you will receive an excessive amount. In the event that an overdose occurs, your doctor will monitor you for any side effects.

If you miss your LYNOZYFIC administration appointment
It is very important to attend all appointments. If you miss an appointment, schedule another one as soon as possible.
If you have any doubts about using this medicine, consult your doctor or nurse.

If you stop receiving LYNOZYFIC
Do not stop treatment with LYNOZYFIC unless you have discussed it with your doctor. Stopping treatment may worsen your condition.
If you have any doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Seek immediate medical help if you experience any of the following serious side effects, which can be severe and in rare cases fatal if not treated correctly and promptly.
Very common (may affect more than 1 in 10 people)

• cytokine release syndrome (CRS), which may include fever, feeling dizzy or lightheaded, chills, difficulty breathing, or rapid heartbeat
• lung infection (pneumonia), with symptoms such as cough, fever, difficulty breathing, or chest pain
• COVID-19 infection, with symptoms such as fever, chills, cough, difficulty breathing, sore throat, fatigue, or new onset loss of taste or smell
• urinary tract infection, with symptoms such as fever, chills, pain or burning sensation when urinating, increased need to urinate, or back pain
• low levels in the blood of antibodies called “immunoglobulins” (hypogammaglobulinemia), which may make infections more likely
• low levels of a type of white blood cells (neutropenia), which may make infections more likely – detected in blood tests

Common (may affect up to 1 in 10 people)

• infusion-related reactions (IRR), which may include fever, feeling dizzy or lightheaded, chills, difficulty breathing, or rapid heartbeat
• signs of a serious immune reaction called “immune effector cell-associated neurotoxicity syndrome” (ICANS); some signs include: difficulty speaking, writing, or understanding things, confusion, feeling less alert or aware, disorientation, or seizures
• low levels of a type of white blood cells accompanied by fever (febrile neutropenia)
• severe infection spreading throughout the body (sepsis)
• CMV infection (may cause severe infections in blood and tissues)

Uncommon (may affect up to 1 in 100 people)

• progressive multifocal leukoencephalopathy (PML). Symptoms of PML may include clumsiness, weakness, difficulty walking, changes in vision, memory loss, or difficulty speaking or thinking

Inform your doctor immediately if you notice any of the serious side effects listed above.
Other side effects
Other side effects are listed below. Inform your doctor or nurse if you experience any of the following side effects.
Very common (may affect more than 1 in 10 people)

• infection of the nose, sinuses, or throat (upper respiratory tract infection)
• low levels of platelets in the blood (thrombocytopenia), which may increase the likelihood of bruising or bleeding
• low levels of red blood cells (anaemia)
• low number of white blood cells (lymphopenia)
• reduced appetite
• increased levels of uric acid in the blood
• low levels of phosphate (hypophosphataemia)
• difficulty sleeping (insomnia)
• alteration in brain function (encephalopathy)
• pain or muscle aches
• pain
• muscle weakness or changes in muscle movement
• headache
• high blood pressure (hypertension)
• cough
• shortness of breath (dyspnoea)
• nasal congestion
• diarrhoea
• constipation
• feeling unwell (nausea)
• vomiting
• rash
• swelling of hands, ankles, or feet (oedema)
• fever
• feeling extremely tired (fatigue)
• chills
• increased levels of creatinine in the blood
• weight loss

Common (may affect up to 1 in 10 people)

• increased blood levels of liver enzymes called transaminases

Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store LYNOZYFIC

LYNOZYFIC will be stored at the hospital or clinic by your doctor.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.". The expiry date refers to the last day of that month.

Unopened vial

• Store in a refrigerator (from 2 °C to 8 °C).
• Do not freeze.
• Keep the vial in the outer packaging to protect the medicine from light.

Infusion solution

Once prepared, the diluted solution should be administered immediately. Chemical and physical in-use stability has been demonstrated for the diluted infusion solution as follows:

• Up to 8 hours at room temperature (from 20 to 25 °C) from preparation to the start of infusion.
• Up to 48 hours under refrigeration (from 2 to 8 °C) from preparation to the start of infusion.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2–8 °C, unless dilution has been carried out under controlled and validated aseptic conditions.
During storage, protect the infusion solution from light.
Your doctor will dispose of any unused medicine appropriately. This will help protect the environment.

6. Contents of the pack and other information

The active substance is linvoseltamab.

• Each vial contains 5 mg of linvoseltamab in 2.5 ml (2 mg/ml).
• Each vial contains 200 mg of linvoseltamab in 10 ml (20 mg/ml).

The other components are histidine, monohydrate histidine hydrochloride, sucrose, polysorbate 80 and water for injections (see “LYNOZYFIC contains polysorbate 80” in section 2).
Description of the appearance of LYNOZYFIC and contents of the pack
LYNOZYFIC concentrate for solution for infusion is supplied as a liquid, from clear to slightly opalescent, colourless to pale yellow, essentially free from particulate matter, provided in a glass vial.
LYNOZYFIC is supplied in two concentrations (5 mg and 200 mg). Each LYNOZYFIC pack contains one vial.
Marketing Authorisation Holder
Regeneron Ireland Designated Activity Company (DAC)
One Warrington Place
Dublin 2, D02 HH27
Ireland
Tel.: +353 (0) 61 533 400
Manufacturer
Regeneron Ireland DAC
Raheen Business Park Ballycummin
Limerick
Ireland
This medicinal product has been granted a marketing authorisation “subject to additional monitoring”. This means that further data on this medicinal product are required. The European Medicines Agency will review new information on this medicinal product annually and this package leaflet will be updated as necessary.
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

The following information is intended exclusively for healthcare professionals:

Procedures for the proper handling and disposal of antineoplastic medicinal products should be considered.

Instructions for dilution

Use aseptic technique when preparing LYNOZYFIC. Each vial is intended for single-dose use only. Discard any unused portion remaining in the vial.
Do not shake the vial.

Visually inspect the solution for particulate matter and discoloration prior to administration. LYNOZYFIC is a liquid ranging from clear to slightly opalescent, colorless to pale yellow, essentially free of particulate matter. Discard the vial if the solution is cloudy, discolored, or contains particulate matter.

Withdraw the required dose from the LYNOZYFIC vial according to Table 1 and transfer it into an intravenous infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection.
LYNOZYFIC is compatible with polyvinyl chloride (PVC) non-di(2-ethylhexyl)phthalate (non-DEHP), polyolefin (PO), or ethylene vinyl acetate (EVA) infusion bags. Gently invert the bag to mix the diluted solution. Do not shake the solution.

Table 1: Volumes of LYNOZYFIC to be added to the infusion bag

After LYNOZYFIC has been diluted as indicated, administer as follows:

• Connect the prepared IV infusion bag containing the final LYNOZYFIC solution to an IV administration set made of PVC, PVC coated with polyethylene (PE), or polyurethane (PU). Use of a polyethersulfone (PES) filter of 0.2 to 5 microns is recommended.
• Prime the IV tubing with LYNOZYFIC up to the end of the line.
• Do not mix LYNOZYFIC with other medicinal products or administer other drugs simultaneously through the same intravenous line.
• At the end of the LYNOZYFIC infusion, flush the infusion line with an adequate volume of sterile 9 mg/ml (0.9%) sodium chloride injection solution to ensure that the entire contents of the infusion bag have been delivered.
• The total infusion time must include the time required for flushing the infusion line.

Once prepared, the diluted solution should be administered immediately. Chemical and physical stability during use has been demonstrated for the diluted infusion solution as follows:

• Up to 8 hours at room temperature (20 to 25 °C) from preparation to start of infusion.
• Up to 48 hours refrigerated at 2 to 8 °C from preparation to start of infusion.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8 °C, unless dilution has been carried out under controlled and validated aseptic conditions.
During storage, protect the infusion solution from light.

Disposal
Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.

ANNEX IV
CONCLUSIONS ON THE GRANTING OF A CONDITIONAL MARKETING AUTHORISATION

Conclusions provided by the European Medicines Agency on:

• Granting of a conditional marketing authorisation

Following assessment of the application for marketing authorisation, the Committee for Medicinal Products for Human Use (CHMP) considers that the benefit-risk balance is favourable and recommends granting a conditional marketing authorisation, as further described in the European Public Assessment Report (EPAR).