LUNSUMIO 1 mg CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Lunsumio 1 mg concentrate for solution for infusion

Lunsumio 30 mg concentrate for solution for infusion

mosunetuzumab

This medicine is subject to additional monitoring, which will help to quickly identify new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on how to report side effects.

Read all of this leaflet carefully before you start using 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.

Contents of the pack

1. What is Lunsumio and what is it used for
2. What you need to know before you use Lunsumio
3. How to use Lunsumio
4. Possible side effects
5. Storage of Lunsumio
6. Contents of the pack and other information

1. What is Lunsumio and what is it 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 type of blood cancer called follicular lymphoma (FL).

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

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

How Lunsumio works

The active substance in Lunsumio, mosunetuzumab, is a monoclonal antibody, a type of protein that binds to specific targets in the body. In this case, mosunetuzumab binds to a target found on B cells, including cancerous B cells, and another target found on ‘T cells’, a different type of white blood cell. The ‘T cells’ are another part of the body's defenses that can destroy invading cells by binding to the two cells together like a bridge. Lunsumio encourages T cells to destroy cancerous B cells. This helps control FL and prevent it from getting worse.

2. What you need to know before you use Lunsumio

Lunsumio must not be given to you

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

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

Warnings and precautions

Talk to your doctor or nurse before you are given Lunsumio if any of the following apply to you (or if you are not sure):

• you have ever had heart, lung, or kidney problems
• you have an infection, or have had a long-lasting or persistent infection in the past
• you need to have a vaccination or know you will need one in the near future

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

Contact your doctor immediately if you get any of the symptoms of the following serious 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.

• Before each infusion, you will be given medicines to help reduce the possible side effects of cytokine release syndrome.
• Hemophagocytic lymphohistiocytosis is a condition where the immune system produces too many cells that fight infection, called histiocytes and lymphocytes. The signs and symptoms can overlap with CRS, your doctor will check if you have this condition if your CRS does not respond to treatment or lasts longer than expected.

• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)– a condition associated with reactions in the nervous system. Symptoms include feeling confused, memory problems, language or judgment problems, disorientation and confusion, often accompanied by hallucinations (seeing, hearing, or feeling things that are not there), and being unable to concentrate.
• Tumor Lysis Syndrome– some people may have unusual levels of certain salts in the blood – caused by the rapid depletion of cancer cells during treatment.
• • Your doctor or nurse will do blood tests to check for this condition. Before each infusion, you will be well-hydrated and given medicines that can help reduce high levels of uric acid. These can help reduce the possible side effects of tumor lysis syndrome.

• Tumor Flare– as your cancer is being destroyed, it can react and seem like your tumor is getting worse – this is called a “tumor flare reaction”
• Infections– you may have signs of infection, which vary depending on where the infection is in the body.

Children and adolescents

This medicine must not be given to children or adolescents under 18 years. This is because there is no information on the use of this medicine 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.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. This is because Lunsumio may affect your unborn baby.

• Do not use Lunsumio during pregnancy, unless after discussing it 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 contraceptive methods during treatment –and for 3 months after the last dose of Lunsumio.

• Talk to your doctor or nurse about suitable contraceptive methods.

Breastfeeding

Do not breastfeed during and up to 3 months after your last treatment. This is because it is not known if any Lunsumio is passed into breast milk and could therefore affect the baby.

Driving and using machines

Lunsumio's influence on the ability to drive and use machines is important. Due to the possible symptoms of ICANS, you should be careful while driving, cycling, or operating heavy or potentially hazardous machinery. If you currently have such symptoms, avoid these activities and contact your doctor, nurse, or pharmacist. See section 4 for more information on side effects.

3. How Lunsumio is administered

Lunsumio is given under the supervision of an experienced doctor. Follow the treatment schedule that your doctor has explained to you. If you are unsure, ask your doctor again.

How Lunsumio is administered

It is given into a vein, as a drip (infusion).

• It is given over 4 hours for the first cycle. Each cycle lasts 21 days, and in the first cycle, you will be given the infusion over 4 hours on day 1, day 8, and day 15.
• If the side effects are not too severe, the dose may be given over 2 hours for subsequent cycles.

Medicines given before treatment with Lunsumio

You will be given other medicines 30 to 60 minutes before receiving Lunsumio. This is to help prevent reactions to the infusion and fever. These other medicines may include:

• Corticosteroids – such as dexamethasone or methylprednisolone
• Paracetamol
• An antihistamine – such as diphenhydramine

How much Lunsumio is given

Lunsumio is usually given in 21-day cycles. The recommended treatment duration is at least 8 cycles of treatment. However, depending on the side effects and how the disease responds to treatment, you may be given up to 17 cycles.

In Cycle 1, you will be given 3 doses of Lunsumio over 21 days:

• Day 1: 1 mg
• Day 8: 2 mg
• Day 15: 60 mg

In Cycle 2, you will be given only one dose:

• Day 1: 60 mg

In Cycles 3 to 17, you will be given only one dose:

• Day 1: 30 mg

If you miss a dose of Lunsumio

If you miss an appointment, make another one as soon as possible. For the treatment to be fully effective, it is very important not to miss any doses.

If you stop treatment with Lunsumio

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

If you have any other questions about 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

Talk to your doctor immediately 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 may include:

• fever (38°C or higher)
• chills or shaking chills
• cold or pale and sweaty skin
• difficulty breathing
• feeling dizzy
• fast or irregular heartbeat
• confusion
• feeling tired or weak
• fainting
• blurred vision
• headache

Hemophagocytic lymphohistiocytosis

Symptoms may include:

• fever
• enlarged liver and/or spleen
• rash
• enlarged lymph nodes
• easy bruising
• kidney problems
• breathing problems
• heart problems

Tumor Lysis Syndrome

Symptoms may include:

• fever
• chills
• feeling sick (nausea and vomiting)
• confusion
• feeling short of breath
• seizures (fits)
• irregular heartbeat
• dark or cloudy urine
• unusual tiredness
• muscle or joint pain

Shown in blood tests

• increased levels of potassium, phosphate, or uric acid – which can cause kidney problems (part of tumor lysis syndrome)

Tumor Flare

Symptoms may include:

• swollen and tender lymph nodes
• chest pain
• cough or difficulty breathing easily
• pain at the tumor site

Infections

Symptoms may include:

• fever
• cough
• chest pain
• tiredness
• shortness of breath
• painful rash
• sore throat
• pain or burning when passing urine
• feeling weak or unwell.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

Symptoms can occur days or weeks after you receive the infusion and may initially be subtle. Symptoms may include:

• confusion/disorientation
• tiredness
• altered mental state
• impaired mental state
• impaired memory

If you get any of these symptoms after treatment with Lunsumio, contact your doctor immediately. You may need medical treatment.

Other side effects

Very common:may affect more than 1 in 10 people

• rash
• itching of the skin
• dry skin
• diarrhea
• headache
• fever
• chills
• cytokine release syndrome

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 can make you more prone to bruising or bleeding (thrombocytopenia)
• low levels of phosphate, potassium, or magnesium
• high levels of alanine aminotransferase in the blood

Common:may affect up to 1 in 10 people

• lung infection
• upper respiratory tract infection (infection of the nose, throat, sinuses)
• urinary tract infection
• fever due to low levels of neutrophils (a type of white blood cell)
• tumor flare
• a severe immune reaction that affects the nervous system (Immune Effector Cell-Associated Neurotoxicity Syndrome)

Shown in blood tests

• increased levels of liver enzymes, which can be a sign of liver problems

Uncommon:may affect up to 1 in 100 people

• a rapid destruction of tumor cells that results in chemical changes in the blood and damage to organs, including the kidneys, heart, and liver (tumor lysis syndrome)
• a condition where the immune system produces too many cells that fight infection, called histiocytes and lymphocytes (hemophagocytic 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. Storage of Lunsumio

Lunsumio will be stored by healthcare professionals in the hospital or clinic. The storage details to be taken into account 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 on the vial after EXP. The expiry date is the last day of the month stated.
• Store in a refrigerator (2°C – 8°C)
• Do not freeze
• The diluted solution must not be stored for more than 24 hours at 2°C – 8°C or 24 hours at room temperature (9°C – 30°C)
• Keep the container in the outer packaging to protect it from light

Your healthcare professional will dispose of any unused medicine properly. This will help protect the environment.

6. Container Content and Additional Information

Composition of Lunsumio

• The active substance is mosunetuzumab.
• Lunsumio 1 mg: each vial contains 1 mg of mosunetuzumab in 1 ml at a concentration of 1 mg/ml.
• Lunsumio 30 mg: each vial contains 30 mg of mosunetuzumab in 30 ml at a concentration of 1 mg/ml.
• The other components are: L-histidine, L-methionine, acetic acid, sucrose, polysorbate 20 (E432), water for injectable preparations.

Appearance of Lunsumio and Container Content

Lunsumio is a concentrate for solution for infusion (sterile concentrate). It is a clear, transparent liquid contained in a glass vial.

Each Lunsumio container contains one vial.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:

This medicinal product has been authorized with a «conditional approval». This approval mechanism means that more information is expected to be obtained for this medicinal product.

The European Medicines Agency will review the new information for this medicinal product at least once a year, and this prospectus will be updated as necessary.

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

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

Instructions for Dilution

1. Remove and discard a volume of sodium chloride 9 mg/ml (0.9%) solution for injection or sodium chloride 4.5 mg/ml (0.45%) solution for injection equal to the volume of Lunsumio required for the patient dose from the infusion bag according to the table below.
2. Remove the required volume of Lunsumio from the vial using a sterile syringe and dilute within the infusion bag. Discard any unused remainder in the vial.

Table 1: Dilution of Lunsumio

1. Gently mix the infusion bag by slowly inverting the bag. Do not shake.
2. Inspect the infusion bag for particles and discard if present.
3. Attach the detachable label from the prospectus to the infusion bag.

Diluted Solution

The product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and would normally not be more than 24 hours at 2°C to 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

Detachable Label

Detach and attach this label to the infusion bag.