Minjuvi: detailed information

Package leaflet: Information for the user

MINJUVI 200 mg powder for concentrate for solution for infusion

tafasitamab
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 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 questions, ask your doctor or pharmacist.
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

What is in this leaflet

What MINJUVI is and what it is used for
What you need to know before using MINJUVI
How to use MINJUVI
Possible side effects
How to store MINJUVI
Contents of the pack and other information

1. What MINJUVI is and what it is used for

What MINJUVI is
MINJUVI contains the active substance tafasitamab. It is a type of protein called a monoclonal antibody, designed to kill tumour cells. This protein works by binding to a specific target on the surface of a type of white blood cells called B cells or B lymphocytes. When tafasitamab binds to the surface of these cells, the cells die.

What MINJUVI is used for
MINJUVI is used to treat adults with the following B-cell blood cancers:

Diffuse large B-cell lymphoma (DLBCL)
Follicular lymphoma (FL).

It is used when the cancer has come back after a relapse (relapsed) or has not responded (refractory) to at least one previous treatment. In relapsed or refractory DLBCL, it is used even if patients are not eligible for stem cell transplant.

Which other medicines MINJUVI is given with
In relapsed or refractory DLBCL, MINJUVI is used in combination with another anticancer medicine called lenalidomide at the beginning of treatment, after which MINJUVI is continued alone.
In relapsed or refractory FL, MINJUVI is used in combination with two other anticancer medicines called lenalidomide and rituximab.

2. What you should know before using MINJUVI

Do not use MINJUVI

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

Warnings and precautions
Talk to your doctor or pharmacist before using MINJUVI if you have an infection or a history of recurrent infections.
You may experience the following during treatment with MINJUVI:

Infusion-related reactions Infusion-related reactions may occur more frequently during the first infusion. Your doctor will monitor you for infusion-related reactions during the infusion of MINJUVI. Inform your doctor immediately if you experience reactions such as fever, chills, flushing, rash, or difficulty breathing within 24 hours after the infusion. Your doctor will administer treatment before each infusion to reduce the risk of infusion-related reactions. If you do not experience reactions, your doctor may decide that you will not need these medications with subsequent infusions.
Reduction in blood cell counts Treatment with MINJUVI may severely reduce the number of certain types of blood cells in the body, such as white blood cells called neutrophils, platelets, and red blood cells. Inform your doctor immediately if you have a fever of 38 °C or higher, or any signs of bruising or bleeding, as these may be signs of such reduction. Your doctor will monitor your blood counts throughout treatment and before starting each treatment cycle.
Infections Serious infections, including those that may lead to death, may occur during and after treatment with MINJUVI. Inform your doctor if you notice signs of infection such as fever of 38 °C or higher, chills, cough, or pain during urination.
Progressive multifocal leukoencephalopathy (PML) PML is a very rare, potentially fatal brain infection. If you experience symptoms such as memory loss, difficulty speaking, difficulty walking, vision problems, or a sensation of numbness or weakness in the face, arm, or leg, inform your doctor immediately. If you experience any of these symptoms before or during treatment with MINJUVI, or notice any changes, inform your doctor immediately, as these may be signs of PML.
Tumour lysis syndrome Some people may develop unusually high levels of certain substances (such as potassium and uric acid) in the blood due to the rapid breakdown of tumour cells during treatment. This is called tumour lysis syndrome. Inform your doctor if you have symptoms such as nausea, vomiting, loss of appetite, fatigue, dark urine, decreased urine output, flank or back pain, muscle cramps, numbness, or palpitations. Your doctor may give you treatment before each infusion to reduce the risk of tumour lysis syndrome and perform blood tests to monitor for tumour lysis syndrome.

Inform your doctor immediately if you notice any of these problems.
Children and adolescents
MINJUVI is not recommended in children and adolescents under 18 years of age, as there is no information available on its use in this age group.
Other medicines and MINJUVI
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The use of live vaccines during treatment with tafasitamab is not recommended.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Contraception Women of childbearing potential are advised to use effective contraception during treatment with MINJUVI and for at least 3 months after the end of treatment.
Pregnancy Do not use MINJUVI during pregnancy and if you are of childbearing potential and not using contraceptive methods. Pregnancy must be excluded before starting treatment. Inform your doctor immediately if you become pregnant or think you may be pregnant during treatment with MINJUVI.

MINJUVI is administered in combination with lenalidomide for up to 12 cycles. Lenalidomide
may cause harm to the unborn child and must not be used during pregnancy or in women of
childbearing potential unless all conditions of the lenalidomide pregnancy prevention program are met. Your doctor will provide further information and recommendations.

Breastfeeding Do not breastfeed during treatment with MINJUVI and for at least 3 months after the last dose. It is not known whether tafasitamab is excreted in human milk.

Driving and using machines
MINJUVI has no effect or negligible effect on the ability to drive and use machines.
However, fatigue has been reported in patients receiving tafasitamab, and this should be taken into consideration when driving or operating machinery.
MINJUVI contains sodium
This medicine contains 37.0 mg of sodium (a key component of table salt) per dose of 5 vials (the dose for an 83 kg patient). This corresponds to 1.85% of the maximum daily dietary intake recommended for an adult.
MINJUVI contains polysorbate
This medicine contains 1 mg of polysorbate 20 in each vial. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use MINJUVI

Treatment will be supervised by a physician experienced in the treatment of cancer. MINJUVI will be administered intravenously as an infusion (drip). During and after the infusion, you will be monitored regularly for the occurrence of any infusion-related adverse reactions. MINJUVI will be given in 28-day cycles. The dose you receive will be based on your body weight and will be calculated by your doctor.

If you have relapsed or refractory diffuse large B-cell lymphoma (DLBCL)
The recommended dose is 12 mg of tafasitamab per kilogram of body weight. This dose is administered as an intravenous infusion according to the following schedule:

Cycle 1: infusion on days 1, 4, 8, 15, and 22 of the cycle
Cycles 2 and 3: infusion on days 1, 8, 15, and 22 of each cycle
Cycle 4 and onwards: infusion on days 1 and 15 of each cycle

Additionally, your doctor will prescribe lenalidomide capsules for up to twelve cycles. The recommended starting dose of lenalidomide is 25 mg once daily on days 1 to 21 of each cycle.
If necessary, your doctor will adjust the starting dose and subsequent dosing.
Treatment with lenalidomide is discontinued after a maximum of twelve combination therapy cycles. Treatment with MINJUVI alone will then continue until disease progression or until you develop unacceptable adverse reactions.

If you have relapsed or refractory follicular lymphoma (FL)
The recommended dose is 12 mg of tafasitamab per kilogram of body weight. This dose is administered as an intravenous infusion according to the following schedule:

Cycles 1 to 3: infusion on days 1, 8, 15, and 22 of each cycle
Cycles 4 to 12: infusion on days 1 and 15 of each cycle

Additionally, your doctor will prescribe:

A dose of rituximab of 375 mg per square meter of body surface area. This dose is administered as an intravenous infusion on days 1, 8, 15, and 22 of cycle 1, and subsequently on day 1 of each cycle from cycle 2 to cycle 5.
Lenalidomide capsules for up to twelve cycles. The recommended starting dose of lenalidomide is 20 mg once daily on days 1 to 21 of each cycle. If necessary, your doctor will adjust the starting dose and subsequent dosing.

Treatment with rituximab is discontinued after a maximum of five combination therapy cycles. Treatment with both MINJUVI and lenalidomide is also discontinued after a maximum of twelve cycles.

If you receive more MINJUVI than you should
As this medicine is administered in a hospital setting under medical supervision, this is unlikely. Inform your doctor if you think you have received more MINJUVI than prescribed.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Immediately inform your doctor or nurse if you notice any of the following serious side effects:
you may need urgent medical treatment. These could be new symptoms or a change in your current symptoms.

Severe infections, possible symptoms: fever, chills, sore throat, cough, shortness of breath, nausea, vomiting, diarrhoea. These may be particularly significant if you have been told that you have a low level of white blood cells called neutrophils.
Pneumonia (lung infection)
Sepsis (blood infection)

Other side effects
Inform your doctor or nurse if you notice any of the following side effects:
Very common (may affect more than 1 in 10 people)

reduction in blood cell counts
- white blood cells, especially a type called neutrophils; possible symptoms: fever of 38 °C or higher, or any sign of infection
- platelets; possible symptoms: unusual bruising or bleeding in the absence of injury or with minor injury
- red blood cells; possible symptoms: paleness of the skin or lips, fatigue, shortness of breath
bacterial, viral or fungal infections, such as respiratory tract infections, bronchitis, lung inflammation, urinary tract infections
rash
itching
infusion-related reaction. Such reactions may occur during infusion of MINJUVI or within 24 hours after the infusion. Possible symptoms include fever, chills, flushing, or difficulty breathing
low blood potassium levels detected by blood tests
muscle cramps
back pain
swelling of arms and/or legs due to fluid retention
weakness, fatigue, general feeling of being unwell
fever
diarrhoea
constipation
abdominal pain
nausea
vomiting
cough
shortness of breath
loss of appetite
headache

Common (may affect up to 1 in 10 people)

worsening of breathing difficulties caused by narrowing of the airways, known as chronic obstructive pulmonary disease (COPD)
abnormal skin sensations such as tingling, pricking, or numbness
skin redness
chills
altered sense of taste
hair loss
abnormal sweating
pain in arms and legs
muscle and joint pain
weight loss
nasal congestion
inflammation of mucous membranes lining organs such as the mouth
low levels of a type of white blood cells called lymphocytes detected in blood tests
an immune system disorder called hypogammaglobulinaemia
in blood tests, low levels of
- calcium
- magnesium
in blood tests, increased levels of
- C-reactive protein, which may indicate inflammation or infection
creatinine, a breakdown product from muscle tissue
liver enzymes: gamma-glutamyltransferase, transaminases
bilirubin, a yellow substance resulting from the breakdown of blood pigment
- a type of skin cancer called basal cell carcinoma

Uncommon (may affect up to 1 in 100 people)

abnormal levels of chemicals in the blood due to rapid destruction of tumour cells during treatment (tumour lysis syndrome)

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

5. How to store MINJUVI

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and carton after EXP/Scad. The expiry date refers to the last day of that month.
Store in the refrigerator (2 °C – 8 °C).
Keep the vial in the outer packaging to protect the medicine from light.
Unused medicine and waste material related to this medicine must be disposed of in accordance with local regulations.

6. Package contents and other information

What MINJUVI contains

The active substance is tafasitamab. One vial contains 200 mg of tafasitamab. After reconstitution, each mL of solution contains 40 mg of tafasitamab.
The other components are sodium citrate dihydrate, citric acid monohydrate, trehalose dihydrate, and polysorbate 20 (see section 2 “MINJUVI contains sodium and polysorbate”).

Description of the appearance of MINJUVI and contents of the pack
MINJUVI is a powder for concentrate for solution for infusion. It is a lyophilised powder, white to slightly yellowish in colour, contained in a clear glass vial with a rubber stopper, aluminium seal, and plastic flip-off cap.
Each pack contains 1 vial.

Marketing Authorisation Holder and Manufacturer
Incyte Biosciences Distribution B.V.
Paasheuvelweg 25
1105 BP Amsterdam
The Netherlands

This medicinal product has been granted a conditional marketing authorisation. This means that additional data on this medicinal product are required.
The European Medicines Agency will review new information on this medicinal product at least annually, and this package leaflet will be updated as necessary.

Further information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.
This leaflet is available in all EU/EEA languages on the website of the European Medicines Agency.

The following information is intended exclusively for healthcare professionals:

MINJUVI is supplied in sterile, preservative-free, single-use vials.
MINJUVI must be reconstituted and diluted prior to intravenous infusion.
Use appropriate aseptic techniques for reconstitution and dilution.

Reconstitution instructions

Determine the tafasitamab dose based on patient weight by multiplying 12 mg by the patient's weight (in kg). Then calculate the number of tafasitamab vials required (each vial contains 200 mg of tafasitamab).
Using a sterile syringe, gently add 5.0 mL of sterile water for injection to each MINJUVI vial. Direct the stream onto the vial walls and not directly onto the lyophilized powder.
Gently swirl the reconstituted solution vial to facilitate dissolution of the lyophilized powder. Do not shake or vigorously invert. Do not remove contents until all solid material is completely dissolved. The lyophilized powder should dissolve within 5 minutes.
The reconstituted solution should appear as a clear, colorless to slightly yellow solution. Visually inspect for particulate matter or discoloration before proceeding. Discard the vial(s) if the solution is cloudy, discolored, or contains visible particles.

Dilution instructions

Use an infusion bag containing 250 mL of 9 mg/mL (0.9%) sodium chloride injection solution.
Calculate the total required volume of the reconstituted 40 mg/mL tafasitamab solution. Remove an equivalent volume from the infusion bag and discard it.
Withdraw the calculated total volume (in mL) of reconstituted tafasitamab solution from the vial(s) and slowly add it to the infusion bag containing 9 mg/mL (0.9%) sodium chloride. Discard any unused tafasitamab remaining in the vial.
The final concentration of the diluted solution must be between 2 mg/mL and 8 mg/mL of tafasitamab.
Gently mix the intravenous bag by slowly inverting it. Do not shake.

Administration instructions

For the first infusion of cycle 1, the intravenous infusion rate should be 70 mL/hour for the first 30 minutes. Afterwards, the rate may be increased to complete the first infusion within a 2.5-hour period.
All subsequent infusions should be administered within 1.5 to 2 hours.
Do not administer other medicinal products concomitantly through the same infusion line.
Do not administer MINJUVI by rapid intravenous injection or bolus administration.

Reconstituted solution (prior to dilution)
Chemical and physical in-use stability has been demonstrated for up to 30 days at a temperature between 2 °C and 8 °C or up to 24 hours at 25 °C.
From a microbiological standpoint, the reconstituted solution should be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user and normally should not exceed 24 hours at temperatures between 2 °C and 8 °C, unless reconstitution was carried out under controlled and validated aseptic conditions. Do not freeze or shake.

Diluted solution (for infusion)
Chemical and physical in-use stability has been demonstrated for up to 14 days at a temperature between 2 °C and 8 °C followed by up to 24 hours at 25 °C.
From a microbiological standpoint, the diluted solution 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 temperatures between 2 °C and 8 °C, unless dilution was carried out under controlled and validated aseptic conditions. Do not freeze or shake.

Unused medicinal product and waste materials derived from this medicinal product must be disposed of in accordance with local regulations.