InfoCons Consumer Protection informs you – Lunsumio – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.  Keep this leaflet. You may need to read it again.  If you have any further questions, ask your doctor, pharmacist or nurse.  If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

ℹ️ 1. What Lunsumio is and what it is used for

Lunsumio contains the active substance mosunetuzumab, which is a type of antibody. This is a cancer medicine. It is used to treat adults who have a blood cancer called follicular lymphoma (FL).

In FL, a type of white blood cells called ‘B-cells’ become cancerous. The abnormal B cells do not work properly and grow too quickly, crowding out the normal B cells in the bone marrow and lymph nodes that help protect you from infection.

Lunsumio is given to patients who have tried at least two previous treatments for FL, when either the cancer has not responded to them, or it has come back again.

How Lunsumio works

The active substance in Lunsumio, mosunetuzumab, is a monoclonal antibody, a type of protein that attaches to specific targets in the body. In this case, mosunetuzumab attaches to a target substance found on B cells, including the cancerous B cells, and another target found on ‘T-cells’, a different type of white blood cell. T cells are another part of the body’s defences that can destroy invading cells.

By attaching the two cells together like a bridge, Lunsumio encourages the T cells to destroy the cancerous B-cells. This helps control the FL and prevent its spread.

⚠️ 2. What you need to know before you use Lunsumio

You must not be given Lunsumio  if you are allergic to mosunetuzumab or any of the other ingredients of this medicine (listed in section 6).

74If you are not sure, talk to your doctor or nurse before you are given Lunsumio.

Warnings and precautions

Talk to your doctor or nurse before you are given Lunsumio if any of the following apply to you (or you are not sure):  you have ever had heart, lung or kidney problems  you have an infection, or have had an infection in the past which lasted a long time or keeps coming back  you are due to have a vaccine or you know you may need to have one in the near future.

If any of the above apply to you (or you are not sure), talk to your doctor or nurse before having this medicine.

Tell your doctor straight away if you get symptoms of any of the side effects listed below during or after treatment with Lunsumio. You may need additional medical treatment. The symptoms of each side effect are listed in section 4.  Cytokine release syndrome (CRS) – a condition associated with medicines that stimulate T cells. o Before each injection, you may be given medicines, which help reduce possible side effects of cytokine release syndrome.  Immune effector cell-associated neurotoxicity syndrome (ICANS) – a condition associated with effects on the nervous system. Symptoms include feeling confused, problems with memory, language or judgement, disorientation and confusion often accompanied by hallucination (seeing, hearing or feeling things that are not there), and not being able to concentrate.  Progressive multifocal leukoencephalopathy (PML) – a serious and fatal brain infection.

Signs and symptoms of PML include memory loss, trouble speaking, difficulty walking, and problems with eyesight. These symptoms may overlap or be similar to the neurologic toxicity symptoms mentioned above.  Haemophagocytic lymphohistiocytosis – a condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes. Signs and symptoms may overlap with CRS, your doctor will check for this condition if your CRS does not respond to treatment or lasts longer than expected.  Tumour lysis syndrome – some people may get unusual levels of some salts in the blood caused by the fast breakdown of cancer cells during treatment. Your doctor or nurse will do blood tests to check for this condition. Before each injection, you should be well-hydrated and may be given medicines that can help reduce high levels of uric acid. These may help reduce possible side effects of tumour lysis syndrome.  Tumour flare – asyour cancer is destroyed, it may react and appear to get worse –this is called ‘tumour flare reaction’.  Infections – you may get signs of infection, which can vary depending on where in the body the infection is.

Children and adolescents

This medicine should not be used in children or adolescents under the age of 18. This is because there is no information about use in this age group.

Other medicines and Lunsumio

Tell your doctor if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription and herbal medicines.

75Pregnancy and breast-feeding It is important to tell your doctor before and during treatment if you are pregnant, think you may be pregnant, or are planning to get pregnant. This is because Lunsumio may affect your unborn baby.  Do not use Lunsumio during pregnancy, unless after discussion with your doctor, it is agreed that the benefits of treatment outweigh any risk to the unborn baby.

Contraception Women who could become pregnant must use effective contraception during treatment –and for 3 months after the last dose of Lunsumio.  Talk to your doctor or nurse about suitable methods of contraception.

Breast-feeding

You must not breast-feed during and for at least 3 months after your last treatment. This is because it is not known whether any Lunsumio passes into breast milk and could therefore affect the baby.

Driving and using machines

Lunsumio has a major influence on your ability to drive, cycle or use any tools or machines. Due to the possible symptoms of ICANS, you should be careful while driving, cycling or using heavy or potentially dangerous machines. If you currently have such symptoms, avoid these activities and contact your doctor, nurse, or pharmacist. See section 4 for more information about side effects.

Lunsumio contains polysorbate

This medicine contains the following amount of polysorbate 20, which is equivalent to 0.6 mg/mL:  Lunsumio 5 mg: each vial contains 0.3 mg of polysorbate 20  Lunsumio 45 mg: each vial contains 0.6 mg of polysorbate 20 Polysorbate 20 may cause allergic reactions. Tell your doctor if you have any known allergies.

💊 3. How Lunsumio is given

Lunsumio is given under the supervision of a doctor experienced in giving such treatments. Follow the treatment schedule explained to you by your doctor. Check with your doctor if you are not sure.

How Lunsumio is given Lunsumio solution for injection (5 mg and 45 mg) It is given as an injection under the skin Medicines given before Lunsumio treatment You may be given other medicines 30 to 60 minutes before you are given Lunsumio. This is to help prevent fever. These other medicines may include:  Corticosteroids –such as dexamethasone or methylprednisolone  Paracetamol  An antihistamine – such as diphenhydramine How much Lunsumio is given In cycle 1, you will be given 3 doses of Lunsumio in the 21 days:  Day 1 :5 mg  Day 8 :45 mg 76 Day 15 :45 mg In cycle 2 to 17, you will be given just one dose:  Day 1 :45 mg If you miss a dose of Lunsumio If you miss an appointment, make another one straight away. For the treatment to be fully effective, it is very important not to miss a dose.

If you stop receiving Lunsumio Do not stop treatment with Lunsumio unless you have discussed this with your doctor. This is because stopping treatment may make your condition worse.

If you have any further questions on the use of this medicine, ask 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

Tell your doctor straight away if you notice any of the symptoms of the following serious side effects.

You may only get one or some of these symptoms.

Cytokine release syndrome Symptoms can include:  fever (38°C or higher)  chills or shaking chills  cold or pale clammy skin  difficulty breathing  feeling dizzy or lightheaded  fast or uneven heartbeat  confusion  feeling very tired or weak  fainting  blurred vision  headache.

Haemophagocytic lymphohistiocytosis Symptoms can include:  fever  enlarged liver and/or spleen  skin rash  lymph node enlargement  easy bruising  kidney abnormalities  breathing problems  heart problems.

Tumour lysis syndrome Symptoms can include:  fever 77 chills  feeling or being sick (nausea and vomiting)  confusion  being short of breath  fits (seizures)  uneven heartbeat  dark or cloudy urine  unusual tiredness  muscle or joint pain.

Shown in blood tests  increase in potassium, phosphate or uric acid –which can cause kidney problems (part of tumour lysis syndrome) Tumour flare Symptoms can include:  tender swollen lymph nodes  chest pain  cough or difficulty breathing easily  pain at the site of the tumour.

Infections Symptoms can include:  fever  cough  chest pain  tiredness  shortness of breath  painful rash  sore throat  burning pain when passing urine  feeling weak or generally unwell.

Immune effector cell-associated neurotoxicity syndrome (ICANS) The symptoms can occur days or weeks after you receive the dose and may initially be subtle.

Symptoms can include:  confusion/disorientation  tiredness  altered mental state  lowered mental state  impaired memory Progressive multifocal leukoencephalopathy (PML) The symptoms may overlap or be similar to the neurologic toxicity symptoms mentioned above.

Symptoms can include:  memory loss  trouble speaking  difficulty walking  problems with eyesight If you have any of these symptoms after treatment with Lunsumio, tell your doctor straight away. You may need medical treatment.

Other side effects

Very common: may affect more than 1 in 10 people

 Rash 78 Itchy skin  Dry skin  Diarrhoea  Headache  Fever  Chills  Cytokine release syndrome  Injection site reaction (only when given under the skin)  Infection of upper airways (infection of nose, throat, sinuses) Shown in blood tests  Low levels of some white blood cells (neutropenia)  Low number of red blood cells, which can cause tiredness and shortness of breath  Low platelet count, which may make you more likely to bruise or bleed (thrombocytopenia)  Low level of phosphate, potassium or magnesium  High level of alanine aminotransferase in the blood

Common: may affect up to 1 in 10 people

 Lung infection  Urinary tract infection  Fever due to low levels of neutrophils (a type of white blood cell)  Tumour flare  A serious immune reaction affecting the nervous system (immune effector cell-associated neurotoxicity syndrome) Shown in blood tests  Increased levels of liver enzymes, which may be a sign of liver problems

Uncommon: may affect up to 1 in 100 people

 A rapid breakdown of tumour cells resulting in chemical changes in the blood and damage to organs, including the kidneys, heart, and liver (tumour lysis syndrome)  A condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes (haemophagocytic lymphohistiocytosis).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V . By reporting side effects, you can help provide more information on the safety of this medicine.

🌡️ 5. How to store Lunsumio

Lunsumio will be stored by the healthcare professionals at the hospital or clinic. The storage details that they must take account of are as follows  Keep this medicine out of the sight and reach of children.  Do not use this medicine after the expiry date which is stated on the carton and the vial after EXP. The expiry date refers to the last day of that month.  Store in a refrigerator (2°C – 8°C).  Do not freeze.  The prepared syringe for subcutaneous injection should be administered immediately. If not used immediately, the capped syringe should not be kept more than 28 days at 2°C – 8°C and 24 hours at 9°C – 30°C.  Keep the container in the outer carton in order to protect from light.

79Your healthcare professional will dispose of any unneeded medicine appropriately. These measures will help protect the environment.

📦 6. Contents of the pack and other information

What Lunsumio contains

 The active substance is mosunetuzumab.  Lunsumio 5 mg: Each vial contains 5 milligrams (mg) mosunetuzumab in 0.5 mL at a concentration of 10 mg/mL.  Lunsumio 45 mg: Each vial contains 45 milligrams (mg) mosunetuzumab in 1 mL at a concentration of 45 mg/mL  The other ingredients are: L-histidine, L-methionine, acetic acid, sucrose, polysorbate 20

(E432), water for injections (see section 2 “Lunsumio contains polysorbate”)

What Lunsumio looks like and contents of the pack

Lunsumio is a solution for injection (sterile solution). It is a clear, colourless to slightly brownish- yellow liquid provided in a glass vial.

Each pack of Lunsumio contains one vial.

Marketing Authorisation Holder

Roche Registration GmbH Emil-Barell-Strasse 1 79639 Grenzach-Wyhlen Germany

Manufacturer

Roche Pharma AG Emil-Barell-Strasse 1 79639 Grenzach-Wyhlen Germany For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Luxembourg/Luxemburg N.V. Roche S.A.

België/Belgique/Belgien Tél/Tel: +32 (0) 2 525 82 11Latvija Roche Latvija SIA Tel: +371 – 6 7039831 България Рош България ЕООД Тел: +359 2 474 5444Lietuva UAB “Roche Lietuva” Tel: +370 5 2546799 Česká republika Roche s. r. O.

Tel: +420 – 2 20382111Magyarország Roche (Magyarország) Kft.

Tel: +36 1 279 4500 80Danmark Roche Pharmaceuticals A/S Tlf.: +45 – 36 39 99 99Nederland Roche Nederland B.V.

Tel: +31 (0) 348 438000 Deutschland Roche Pharma AG Tel: +49 (0) 7624 140Norge Roche Norge AS Tlf: +47 – 22 78 90 00 Eesti Roche Eesti OÜ Tel: + 372 – 6 177 380Österreich Roche Austria GmbH Tel: +43 (0) 1 27739 Ελλάδα , Κύπρος Roche (Hellas) A.E.

Ελλάδα Τηλ: +30 210 61 66 100Polska Roche Polska Sp.z o.o.

Tel: +48 – 22 345 18 88 España Roche Farma S.A.

Tel: +34 – 91 324 81 00Portugal Roche Farmacêutica Química, Lda Tel: +351 – 21 425 70 00 France Roche Tél: +33 (0) 1 47 61 40 00România Roche România S.R.L.

Tel: +40 21 206 47 01 Hrvatska Roche d.o.o.

Tel: +385 1 4722 333Slovenija Roche farmacevtska družba d.o.o.

Tel: +386 – 1 360 26 00 Ireland, Malta Roche Products (Ireland) Ltd.

Ireland, L-Irlanda Tel: +353 (0) 1 469 0700Slovenská republika Roche Slovensko, s.r.o.

Tel: +421 – 2 52638201 Ísland Roche Pharmaceuticals A/S c/o Icepharma hf Sími: +354 540 8000Suomi/Finland Roche Oy Puh/Tel: +358 (0) 10 554 500 Italia Roche S.p.A.

Tel: +39 – 039 2471Sverige Roche AB Tel: +46 (0) 8 726 1200

This leaflet was last revised in

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

81The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu.

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🩺 Information intended for healthcare professionals only

Procedures for proper handling and disposal of anticancer medicinal products should be considered Instructions for preparation 1. Retrieve one 5 mg or 45 mg Lunsumio vial from the refrigerator. DO NOT shake the vial.

2. Withdraw the required volume of Lunsumio solution from the vial into a syringe.

3. Label the syringe with the product name, dose (5 mg or 45 mg), date and time.

4. Apply the peel-off label from the package leaflet to the syringe.

5. Discard the vial and any unused portion of Lunsumio in accordance with the local requirements.

Prepared Syringe Once transferred from the vial to the syringe, Lunsumio solution for injection should be injected immediately because the medicine does not contain any antimicrobial-preservative. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless preparation has taken place in controlled and validated aseptic conditions.

If Lunsumio solution for injection is transferred from the vial to the syringe under controlled and validated aseptic conditions, the medicine in the capped syringe can be stored in the refrigerator at 2°C to 8°C for up to 28 days protected from light and/or at 9°C to 30°C for up to 24 hours at ambient light.

If using the 5 mg/0.5 mL configuration Peel-off label Peel and apply this label to the syringe If using the 45 mg/mL configuration Peel-off label Peel and apply this label to the syringe 83ANNEX IV Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s) 84Scientific conclusions Taking into account the PRAC Assessment Report on the PSUR(s) for mosunetuzumab, the scientific conclusions of PRAC are as follows:

In view of published PRAC recommendation on the reviewed data on safety and efficacy included in this PSUR, the PRAC concluded that the product information of mosunetuzumab should be amended accordingly.

Having reviewed the PRAC recommendation, the CHMP agrees with the PRAC overall conclusions and grounds for recommendation.

Grounds for the variation to the terms of the marketing authorisation(s) On the basis of the scientific conclusions for mosunetuzumab the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing mosunetuzumab is unchanged subject to the proposed changes to the product information The CHMP recommends that the terms of the marketing authorisation(s) should be varied.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Lunsumio (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/22/1649).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.