Besponsa

European Union - English - EMA (European Medicines Agency)

Active ingredient:
inotuzumab ozogamicin
Available from:
Pfizer Europe MA EEIG
ATC code:
L01XC
INN (International Name):
inotuzumab ozogamicin
Therapeutic group:
Antineoplastic agents,
Therapeutic area:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Therapeutic indications:
Besponsa is indicated as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL). Adult patients with Philadelphia chromosome positive (Ph+) relapsed or refractory B cell precursor ALL should have failed treatment with at least 1 tyrosine kinase inhibitor (TKI).
Product summary:
Revision: 8
Authorization status:
Authorised
Authorization number:
EMEA/H/C/004119
Authorization date:
2017-06-28
EMEA code:
EMEA/H/C/004119

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Patient Information leaflet Patient Information leaflet - Bulgarian

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Read the complete document

B. PACKAGE LEAFLET

Package leaflet: Information for the user

BESPONSA 1 mg powder for concentrate for solution for infusion

inotuzumab ozogamicin

This medicine is subject to additional monitoring. This will allow quick identification of new

safety information. You can help by reporting any side effects you may get. See the end of section 4

for 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.

What is in this leaflet

What BESPONSA is and what it is used for

What you need to know before you are given BESPONSA

How BESPONSA is given

Possible side effects

How to store BESPONSA

Contents of the pack and other information

1. What BESPONSA is and what it is used for

The active ingredient in BESPONSA is inotuzumab ozogamicin. This belongs to a group of medicines

that target cancer cells. These medicines are called antineoplastic agents.

BESPONSA is used to treat adults with acute lymphoblastic leukaemia. Acute lymphoblastic

leukaemia is a cancer of blood where you have too many white blood cells. BESPONSA is intended

for the treatment of acute lymphoblastic leukaemia for adult patients who have previously tried other

treatments and for whom those treatments have failed.

BESPONSA acts by attaching to cells with a protein called CD22. Lymphoblastic leukaemia cells

have this protein. Once attached to the lymphoblastic leukaemia cells, the medicine delivers a

substance into the cells that interferes with the cells’ DNA and eventually kills them.

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

Do not use BESPONSA if you

are allergic to inotuzumab ozogamicin or any of the other ingredients of this medicine (listed

in section 6).

have previously had severe venoocclusive disease (a condition in which the blood vessels in

the liver become damaged and blocked by blood clots) which was confirmed or have ongoing

venoocclusive disease.

have serious ongoing liver disease, e.g., cirrhosis (a condition in which the liver does not

function properly due to long-term damage), nodular regenerative hyperplasia (a condition

with signs and symptoms of portal hypertension that can be caused by chronic use of

medicines), active hepatitis (a disease characterised by inflammation of the liver).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using BESPONSA if you:

have a history of liver problems or liver diseases or if you have signs and symptoms of a

serious condition called hepatic venoocclusive disease, a condition in which the blood vessels

in the liver become damaged and blocked by blood clots. Venoocclusive disease may be fatal

and is associated with rapid weight gain, pain in the upper right side of your abdomen (belly),

increase in the size of the liver, build-up of fluid causing abdominal swelling, and blood tests

showing increases in bilirubin and/or liver enzymes (that may result in yellowing of the skin

or eyes). This condition may occur during treatment with BESPONSA or after subsequent

treatment with a stem cell transplant. A stem cell transplant is a procedure to transplant

another person’s stem cells (cells which develop into new blood cells) into your bloodstream.

This procedure may take place if your disease responds completely to treatment.

have signs or symptoms of a low number of blood cells known as neutrophils (sometimes

accompanied with fever), red blood cells, white blood cells, lymphocytes, or a low number of

blood components known as platelets; these signs and symptoms include developing an

infection or fever or bruising easily or getting frequent nose bleeds.

have signs and symptoms of an infusion related reaction, such as fever and chills or breathing

problems during or shortly after the BESPONSA infusion.

have signs and symptoms of tumour lysis syndrome, which may be associated with symptoms

in the stomach and intestines (for example, nausea, vomiting, diarrhoea), heart (for example,

changes in the rhythm), kidney (for example, decreased urine, blood in urine), and nerves and

muscles (for example, muscular spasms, weakness, cramps), during or shortly after the

BESPONSA infusion.

have a history of, or tendency to have, QT interval prolongation (a change in electrical activity

of the heart that can cause serious irregular heart rhythms), are taking medicines that are

known to prolong QT interval, and/or have abnormal electrolyte (e.g., calcium, magnesium,

potassium) levels.

have elevations in amylase or lipase enzymes that may be a sign of problems with your

pancreas or liver and gallbladder or bile ducts.

Tell your doctor, pharmacist or nurse immediately if you became pregnant during the period of

treatment with BESPONSA and for up to 8 months after finishing treatment.

Your doctor will take regular blood tests to monitor your blood counts during treatment with

BESPONSA. See also section 4.

During treatment, especially in the first few days after starting treatment, your white blood cell count

may be severely lowered (neutropenia), which may be accompanied by fever (febrile neutropenia).

During treatment, especially in the first few days after starting treatment, you may have raised liver

enzymes. Your doctor will take regular blood tests to monitor your liver enzymes during treatment

with BESPONSA.

Treatment with BESPONSA may prolong QT interval (a change in electrical activity of the heart that

can cause serious irregular heart rhythms). Your doctor will take an electrocardiogram (ECG) and

blood tests to measure electrolytes (e.g., calcium, magnesium, potassium) before the first dose of

BESPONSA and repeat these tests during treatment. See also section 4.

Your doctor will also monitor for signs and symptoms of tumour lysis syndrome after you receive

BESPONSA. See also section 4.

Children and adolescents

BESPONSA should not to be used in children and adolescents under 18 years of age because no data

are available in this population.

Other medicines and BESPONSA

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines. This includes medicines obtained without a prescription and herbal medicines.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor or nurse for advice before taking this medicine.

Contraception

You must avoid becoming pregnant or fathering a child. Women must use effective contraception

during treatment and for at least 8 months after the last dose of treatment. Men must use effective

contraception during treatment and for at least 5 months after the last dose of treatment.

Pregnancy

The effects of BESPONSA in pregnant women are not known, but based on its mechanism of action

BESPONSA may harm your unborn baby. You should not use BESPONSA during pregnancy, unless

your doctor thinks that it is the best medicine for you.

Contact your doctor immediately if you or your partner becomes pregnant during the period of

treatment with this medicine.

Fertility

Men and women should seek advice regarding fertility preservation before treatment.

Breast-feeding

If you need treatment with BESPONSA, you must stop breast-feeding during treatment and for at least

2 months after treatment. Talk to your doctor.

Driving and using machines

If you feel unusually tired (this is a very common side effect of BESPONSA), you should not drive or

use machines.

BESPONSA contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per 1 mg inotuzumab ozogamicin, that is to

say essentially ‘sodium-free.’

3. How BESPONSA is given

Always use this medicine exactly as your doctor, pharmacist, or nurse has told you. Check with your

doctor, pharmacist or nurse if you are not sure.

How BESPONSA is given

Your doctor will decide on the correct dose.

A doctor or nurse will give you BESPONSA through a drip in your vein (intravenous

infusion) which will run for 1 hour.

Each dose is given weekly and each treatment cycle is 3 doses.

If the medicine works well and you are going to receive a stem cell transplant (see section 2),

you may receive 2 cycles or a maximum of 3 cycles of treatment.

If the medicine works well, but you are not going to receive a stem cell transplant (see section

2), you may receive up to a maximum of 6 cycles of treatment.

If you do not respond to the medicine within 3 cycles, your treatment will be stopped.

Your doctor may change your dose, interrupt, or completely stop treatment with BESPONSA

if you have certain side effects.

Your doctor may lower your dose based on your response to treatment.

Your doctor will do blood tests during the treatment to check for side effects and for response

to treatment.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

Medicines given before treatment with BESPONSA

Before your treatment with BESPONSA, you will be given other medicines (pre-medications) to help

reduce infusion reactions and other possible side effects. These may include corticosteroids (e.g.,

dexamethasone), antipyretics (medicines to reduce fever), and antihistamines (medicines to reduce

allergic reactions).

Before your treatment with BESPONSA, you may be given medicines and be hydrated to prevent

tumour lysis syndrome from occurring. Tumour lysis syndrome is associated with a variety of

symptoms in the stomach and intestines (for example, nausea, vomiting, diarrhoea), heart (for

example, changes in the rhythm), kidney (for example, decreased urine, blood in urine), and nerves

and muscles (for example, muscular spasms, weakness, cramps).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of

these side effects may be serious.

Tell your doctor immediately if you have signs and symptoms of any of the following serious side

effects:

infusion related reaction (see section 2); signs and symptoms include fever and chills or

breathing problems during or shortly after the BESPONSA infusion.

venoocclusive liver disease (see section 2); signs and symptoms include rapid weight gain,

pain in the upper right side of your abdomen, increase in the size of the liver, accumulation of

fluid causing abdominal swelling, and increases in bilirubin and/or liver enzymes (that may

result in yellowing of the skin or eyes).

low number of blood cells known as neutrophils, (sometimes accompanied with fever), red

blood cells, white blood cells, lymphocytes, or low number of blood components known as

platelets (see section 2); signs and symptoms include developing an infection or fever or

bruising easily or getting nose bleeds on a regular basis.

tumour lysis syndrome (see section 2); this may be associated with a variety of symptoms in

the stomach and intestines (for example, nausea, vomiting, diarrhoea), heart (for example,

changes in the rhythm), kidney (for example, decreased urine, blood in urine), and nerves and

muscles (for example, muscular spasms, weakness, cramps).

QT interval prolongation (see section 2); signs and symptoms include a change in electrical

activity of the heart that can cause serious irregular heart rhythms. Tell your doctor if you have

symptoms, such as dizziness, lightheadedness or fainting.

Other side effects may include:

Very common: may affect more than 1 in 10 people

Infections

Reduced number of white blood cells which may result in general weakness and a tendency to

develop infections

Reduced number of lymphocytes (a type of white blood cells) which may result in a tendency

to develop infections

Reduced number of red blood cells which may result in fatigue and shortness of breath

Decreased appetite

Headache

Bleeding

Pain in the abdomen

Vomiting

Diarrhoea

Nausea

Mouth inflammation

Constipation

Raised bilirubin level which may result in a yellowish colour in the skin, eyes, and other

tissues

Fever

Chills

Fatigue

High levels of liver enzymes (which can be indicators of liver injury) in the blood

Common: may affect up to 1 in 10 people

Reduction in the number of various types of blood cells

Excess of uric acid in the blood

Excessive accumulation of fluid in the abdomen

Swelling of the abdomen

Changes in heart rhythm (may show on electrocardiogram)

Abnormally high levels of amylase (an enzyme needed for digestion and conversion of starch

into sugars) in the blood

Abnormally high levels of lipase (an enzyme needed to process dietary fat) in the blood

Hypersensitivity

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.

How to store BESPONSA

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 vial label and carton after EXP.

The expiry date refers to the last day of that month.

Unopened vial

Store in a refrigerator (2 °C-8 °C).

Store in the original carton in order to protect from light.

Do not freeze.

Reconstituted solution

Use immediately or store in a refrigerator (2 °C-8 °C) for up to 4 hours.

Protect from light.

Do not freeze.

Diluted solution

Use immediately or store at room temperature (20 °C-25 °C) or in a refrigerator (2 °C-8 °C). The

maximum time from reconstitution through the end of administration should be ≤ 8 hours, with

≤ 4 hours between reconstitution and dilution.

Protect from light.

Do not freeze.

This medicine should be inspected visually for particulate matter and discolouration prior to

administration. If particles or discolouration are observed, do not use.

Do not throw away any medicines via wastewater or household waste. Ask your doctor how to throw

away medicines you no longer use. These measures will help protect the environment.

Contents of the pack and other information

What BESPONSA contains

The active substance is inotuzumab ozogamicin. Each vial contains 1 mg inotuzumab

ozogamicin. After reconstitution, 1 mL of solution contains 0.25 mg inotuzumab ozogamicin.

The other ingredients are sucrose, polysorbate 80, sodium chloride, and tromethamine (see

section 2).

What BESPONSA looks like and contents of the pack

BESPONSA is a powder for concentrate for solution for infusion.

Each pack of BESPONSA contains:

1 glass vial containing a white to off-white lyophilised cake or powder.

Marketing Authorisation Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer

Pfizer Service Company BV

Hoge Wei 10

B-1930, Zaventem

Belgium

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder:

Belgique/België/Belgien

Pfizer S.A. / N.V.

Tél/Tel: +32 (0)2 554 62 11

Lietuva

Pfizer Luxembourg SARL filialas Lietuvoje

Tel: + 370 52 51 4000

България

Пфайзер Люксембург САРЛ, Клон

България

Тел.: +359 2 970 4333

Luxembourg/Luxemburg

Pfizer S.A.

Tél/Tel: +32 (0)2 554 62 11

Česká republika

Pfizer, spol. s r.o.

Tel: +420 283 004 111

Magyarország

Pfizer Kft.

Tel: +36-1-488-37-00

Danmark

Pfizer ApS

Tlf: +45 44 20 11 00

Malta

Vivian Corporation Ltd.

Tel: +356 21344610

Deutschland

Pfizer Pharma GmbH

Tel: +49 (0)30 550055 51000

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Ελλάδα

Pfizer Ελλάς A.E.

Τηλ: +30 210 6785 800

Österreich

Pfizer Corporation Austria Ges.m.b.H.

Tel: +43 (0)1 521 15-0

España

Pfizer, S.L.

Tel: +34 91 490 99 00

Polska

Pfizer Polska Sp. z o.o.

Tel: +48 22 335 61 00

France

Pfizer

Tel: +33 (0)1 58 07 34 40

Portugal

Laboratórios Pfizer, Lda.

Tel: +351 21 423 5500

Hrvatska

Pfizer Croatia d.o.o.

Tel: + 385 1 3908 777

România

Pfizer Romania S.R.L.

Tel: +40 (0) 21 207 28 00

Ireland

Pfizer Healthcare Ireland

Tel: 1800 633 363 (toll free)

+44 (0)1304 616161

Slovenija

Pfizer Luxembourg SARL

Pfizer, podružnica za svetovanje s področja

farmacevtske dejavnosti, Ljubljana

Tel: + 386 (0)1 52 11 400

Ísland

Icepharma hf.

Sími: +354 540 8000

Slovenská republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: + 421 2 3355 5500

Italia

Pfizer S.r.l.

Tel: +39 06 33 18 21

Suomi/Finland

Pfizer Oy

Puh/Tel: +358 (0)9 43 00 40

Κύπρος

Pfizer Ελλάς Α.Ε. (Cyprus Branch)

Τηλ: +357 22 817690

Sverige

Pfizer AB

Tel: +46 (0)8 550-520 00

Latvija

Pfizer Luxembourg SARL filiāle Latvijā

Tel: + 371 670 35 775

United Kingdom (Northern Ireland)

Pfizer Limited

Tel: +44 (0) 1304 616161

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

The following information is intended for healthcare professionals only. For full information on

dosage and dose modifications please refer to the Summary of Product Characteristics.

Method of administration

BESPONSA is for intravenous use. The infusion must be administered over 1 hour.

Do not administer BESPONSA as an intravenous push or bolus.

BESPONSA must be reconstituted and diluted before administration.

BESPONSA should be administered in 3- to 4-week cycles.

For patients proceeding to a haematopoietic stem cell transplant (HSCT), the recommended duration

of treatment is 2 cycles. A third cycle may be considered for those patients who do not achieve a

CR/CRi and MRD negativity after 2 cycles. For patients not proceeding to HSCT, a maximum of

6 cycles, may be administered. Any patients who do not achieve a CR/CRi within 3 cycles should

discontinue treatment (see Summary of Product Characteristics section 4.2).

The table below shows the recommended dosing regimens.

For the first cycle, the recommended total dose for all patients is 1.8 mg/m

per cycle, administered as

3 divided doses on Days 1 (0.8 mg/m

), 8 (0.5 mg/m

), and 15 (0.5 mg/m

). Cycle 1 is 3 weeks in

duration, but may be extended to 4 weeks if the patient achieves a CR or CRi, and/or to allow recovery

from toxicity.

For subsequent cycles, the recommended total dose is 1.5 mg/m

per cycle administered as 3 divided

doses on Days 1 (0.5 mg/m

), 8 (0.5 mg/m

), and 15 (0.5 mg/m

) for patients who achieve a CR/CRi or

1.8 mg/m

per cycle given as 3 divided doses on Days 1 (0.8 mg/m

), 8 (0.5 mg/m

), and

15 (0.5 mg/m

) for patients who do not achieve a CR/CRi. Subsequent cycles are 4 weeks in duration.

Dosing regimen for Cycle 1 and subsequent cycles depending on response to treatment

Day 1

Day 8

Day 15

Dosing regimen for Cycle 1

All patients:

Dose (mg/m

Cycle length

21 days

Dosing regimen for subsequent cycles depending on response to treatment

Dosing regimen for Cycle 1 and subsequent cycles depending on response to treatment

Day 1

Day 8

Day 15

Patients who have achieved a CR

or CRi

Dose (mg/m

Cycle length

28 days

Patients who have not achieved a CR

or CRi

Dose (mg/m

Cycle length

28 days

Abbreviations: ANC=absolute neutrophil counts; CR=complete remission; CRi=complete remission with

incomplete haematological recovery.

+/- 2 days (maintain a minimum of 6 days between doses).

For patients who achieve a CR/CRi, and/or to allow for recovery from toxicity, the cycle length may be

extended up to 28 days (i.e. 7-day treatment-free interval starting on Day 21).

CR is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukaemic blasts, full

recovery of peripheral blood counts (platelets ≥ 100 × 10

/L and ANC ≥ 1 × 10

/L) and resolution of any

extramedullary disease.

CRi is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukaemic blasts,

incomplete recovery of peripheral blood counts (platelets < 100 × 10

/L and/or ANC < 1 × 10

/L) and

resolution of any extramedullary disease.

7-day treatment-free interval starting on Day 21.

Instructions for reconstitution, dilution, and administration

Use appropriate aseptic technique for the reconstitution and dilution procedures. Inotuzumab

ozogamicin (which has a density of 1.02 g/mL at 20 °C/68 °F) is light sensitive and should be

protected from ultraviolet light during reconstitution, dilution, and administration.

The maximum time from reconstitution through the end of administration should be ≤ 8 hours, with ≤

4 hours between reconstitution and dilution.

Reconstitution:

Calculate the dose (mg) and number of vials of BESPONSA required.

Reconstitute each 1 mg vial with 4 mL of water for injection, to obtain a single-use solution of

0.25 mg/mL of BESPONSA.

Gently swirl the vial to aid dissolution. Do not shake.

Inspect the reconstituted solution for particulates and discolouration. The reconstituted

solution must be clear to slightly cloudy, colourless, and essentially free of visible foreign

matter. If particles or discolouration are observed, do not use.

BESPONSA contains no bacteriostatic preservatives. The reconstituted solution must be used

immediately. If the reconstituted solution cannot be used immediately, it may be stored in a

refrigerator (2 °C-8 °C) for up to 4 hours. Protect from light and do not freeze.

Dilution:

Calculate the required volume of the reconstituted solution needed to obtain the appropriate

dose according to patient body surface area. Withdraw this amount from the vial(s) using a

syringe. Protect from light. Discard any unused reconstituted solution left in the vial.

Add the reconstituted solution to an infusion container with sodium chloride 9 mg/mL (0.9%)

solution for injection, to a total nominal volume of 50 mL. The final concentration should be

between 0.01 and 0.1 mg/mL. Protect from light. An infusion container made of polyvinyl

chloride (PVC) (di(2-ethylhexyl)phthalate [DEHP]- or non-DEHP-containing), polyolefin

(polypropylene and/or polyethylene), or ethylene vinyl acetate (EVA) is recommended.

Gently invert the infusion container to mix the diluted solution. Do not shake.

The diluted solution must be used immediately, stored at room temperature (20 °C-25 °C) or

in a refrigerator

2 °C-8 °C). The maximum time from reconstitution through the end of

Read the complete document

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

This medicinal product is subject to additional monitoring. This will allow quick identification of

new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

See section 4.8 for how to report adverse reactions.

NAME OF THE MEDICINAL PRODUCT

BESPONSA 1 mg powder for concentrate for solution for infusion

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 1 mg inotuzumab ozogamicin.

After reconstitution (see section 6.6), 1 mL of solution contains 0.25 mg inotuzumab ozogamicin.

Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) composed of a recombinant humanised

IgG4 kappa CD22-directed monoclonal antibody (produced in Chinese hamster ovary cells by

recombinant DNA technology) that is covalently linked to N-acetyl-gamma-calicheamicin

dimethylhydrazide.

For the full list of excipients, see section 6.1.

PHARMACEUTICAL FORM

Powder for concentrate for solution for infusion.

White to off-white, lyophilised cake or powder.

CLINICAL PARTICULARS

Therapeutic indications

BESPONSA is indicated as monotherapy for the treatment of adults with relapsed or refractory

CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL). Adult patients with

Philadelphia chromosome positive (Ph

) relapsed or refractory B cell precursor ALL should have

failed treatment with at least 1 tyrosine kinase inhibitor (TKI).

Posology and method of administration

BESPONSA should be administered under the supervision of a physician experienced in the use of

cancer therapy and in an environment where full resuscitation facilities are immediately available.

When considering the use of BESPONSA as a treatment for relapsed or refractory B cell ALL,

baseline CD22 positivity of > 0% using a validated and sensitive assay is required prior to initiating

treatment (see section 5.1).

For patients with circulating lymphoblasts, cytoreduction with a combination of hydroxyurea, steroids,

and/or vincristine to a peripheral blast count ≤ 10,000/mm

is recommended prior to the first dose.

Pre-medication with a corticosteroid, antipyretic, and antihistamine is recommended prior to dosing

(see section 4.4).

For patients with a high tumour burden, pre-medication to reduce uric acid levels and hydration is

recommended prior to dosing (see section 4.4).

Patients should be observed during, and for at least 1 hour after the end of infusion for symptoms of

infusion related reactions (see section 4.4).

Posology

BESPONSA should be administered in 3- to 4-week cycles.

For patients proceeding to haematopoietic stem cell transplant (HSCT), the recommended duration of

treatment is 2 cycles. A third cycle may be considered for those patients who do not achieve a

complete remission (CR) or complete remission with incomplete haematological recovery (CRi) and

minimal residual disease (MRD) negativity after 2 cycles (see section 4.4). For patients not proceeding

to HSCT, a maximum of 6 cycles may be administered. Any patients who do not achieve a CR/CRi

within 3 cycles should discontinue treatment.

Table 1 shows the recommended dosing regimens.

For the first cycle, the recommended total dose of BESPONSA for all patients is 1.8 mg/m

per cycle,

given as 3 divided doses on Days 1 (0.8 mg/m

), 8 (0.5 mg/m

), and 15 (0.5 mg/m

). Cycle 1 is

3 weeks in duration but may be extended to 4 weeks if the patient achieves a CR or CRi, and/or to

allow recovery from toxicity.

For subsequent cycles, the recommended total dose of BESPONSA is 1.5 mg/m

per cycle given as

3 divided doses on Days 1 (0.5 mg/m

), 8 (0.5 mg/m

), and 15 (0.5 mg/m

) for patients who achieve a

CR/CRi or 1.8 mg/m

per cycle given as 3 divided doses on Days 1 (0.8 mg/m

), 8 (0.5 mg/m

), and

15 (0.5 mg/m

) for patients who do not achieve a CR/CRi. Subsequent cycles are 4 weeks in duration.

Table 1.

Dosing regimen for Cycle 1 and subsequent cycles depending on response to

treatment

Day 1

Day 8

Day 15

Dosing regimen for Cycle 1

All patients:

Dose (mg/m

Cycle length

21 days

Dosing regimen for subsequent cycles depending on response to treatment

Patients who have achieved a CR

or CRi

Dose (mg/m

Cycle length

28 days

Patients who have not achieved a CR

or CRi

Dose (mg/m

Cycle length

28 days

Abbreviations: ANC=absolute neutrophil counts; CR=complete remission; CRi=complete remission with

incomplete haematological recovery.

+/- 2 days (maintain minimum of 6 days between doses).

For patients who achieve a CR/CRi, and/or to allow for recovery from toxicity, the cycle length may be

extended up to 28 days (i.e. 7-day treatment-free interval starting on Day 21).

CR is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukaemic blasts, full

recovery of peripheral blood counts (platelets ≥ 100 × 10

/L and ANC ≥ 1 × 10

/L) and resolution of any

extramedullary disease.

CRi is defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukaemic blasts,

incomplete recovery of peripheral blood counts (platelets < 100 × 10

/L and/or ANC < 1 × 10

/L) and

resolution of any extramedullary disease.

7-day treatment-free interval starting on Day 21.

Dose modifications

Dose modification of BESPONSA may be required based on individual safety and tolerability (see

section 4.4). Management of some adverse drug reactions may require dosing interruptions and/or

dose reductions, or permanent discontinuation of BESPONSA (see sections 4.4 and 4.8). If the dose is

reduced due to BESPONSA-related toxicity, the dose should not be re-escalated.

Table 2 and Table 3 show the dose modification guidelines for haematological and

non-haematological toxicities, respectively. BESPONSA doses within a treatment cycle (i.e. Days 8

and/or 15) do not need to be interrupted due to neutropenia or thrombocytopenia, but dosing

interruptions within a cycle are recommended for non-haematological toxicities.

Table 2.

Dose modifications for haematological toxicities at the start of a treatment cycle

(Day 1)

Haematological toxicity

Toxicity and dose modification(s)

Levels prior to BESPONSA

treatment:

ANC was ≥ 1 × 10

If ANC decreases, interrupt the next cycle of treatment until

recovery of ANC to ≥ 1 × 10

Platelet count was

≥ 50 × 10

If platelet count decreases, interrupt the next cycle of treatment

until platelet count recovers to ≥ 50 × 10

ANC was < 1 × 10

/L and/or

platelet count was

< 50 × 10

If ANC and/or platelet count decreases, interrupt the next cycle

of treatment until at least one of the following occurs:

- ANC and platelet count recover to at least baseline levels for

the prior cycle, or

- ANC recovers to ≥ 1 × 10

/L and platelet count recovers

to ≥ 50 × 10

, or

- Stable or improved disease (based on most recent bone

marrow assessment) and the ANC and platelet count

decrease is considered to be due to the underlying disease

(not considered to be BESPONSA-related toxicity).

Abbreviation: ANC=absolute neutrophil count.

Platelet count used for dosing must be independent of blood transfusion.

Table 3.

Dose modifications for non-haematological toxicities at any time during treatment

Non-haematological toxicity

Dose modification(s)

VOD/SOS or other severe liver

toxicity

Permanently discontinue treatment (see section 4.4).

Total bilirubin > 1.5 × ULN and

AST/ALT > 2.5 × ULN

Interrupt the dosing until recovery of total bilirubin to

≤ 1.5 × ULN and AST/ALT to ≤ 2.5 × ULN prior to each dose

unless due to Gilbert’s disease or haemolysis. Permanently

discontinue treatment if total bilirubin does not recover to

≤ 1.5 × ULN or AST/ALT does not recover to ≤ 2.5 × ULN

(see section 4.4).

Infusion related reaction

Interrupt the infusion and institute appropriate medical

management. Depending on the severity of the infusion related

reaction, consider discontinuation of the infusion or

administration of steroids and antihistamines. For severe or

life-threatening infusion reactions, permanently discontinue

treatment (see section 4.4).

Grade ≥ 2

non-haematological

toxicity (BESPONSA-related)

Interrupt treatment until recovery to Grade 1 or pre-treatment

grade levels prior to each dose.

Table 3.

Dose modifications for non-haematological toxicities at any time during treatment

Non-haematological toxicity

Dose modification(s)

Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal;

VOD/SOS=venoocclusive disease/sinusoidal obstruction syndrome.

Severity grade according to

National Cancer Institute Common Terminology Criteria for Adverse Events

(NCI CTCAE) version 3.0.

Table 4 shows the dose modification guidelines depending on the duration of dosing interruptions due

to toxicity.

Table 4.

Dose modifications depending on duration of dosing interruption due to toxicity

Duration of dosing

interruption due to toxicity

Dose modification(s)

< 7 days (within a cycle)

Interrupt the next dose (maintain a minimum of 6 days

between doses).

≥ 7 days

Omit the next dose within the cycle.

≥ 14 days

Once adequate recovery is achieved, decrease the total dose by

25% for the subsequent cycle. If further dose modification is

required, then reduce the number of doses to 2 per cycle for

subsequent cycles. If a 25% decrease in the total dose followed

by a decrease to 2 doses per cycle is not tolerated, then

permanently discontinue treatment.

> 28 days

Consider permanent discontinuation of BESPONSA.

Special populations

Elderly

No adjustment to the starting dose is required based on age (see section 5.2).

Hepatic impairment

No adjustment to the starting dose is required in patients with hepatic impairment defined by total

bilirubin ≤ 1.5 × upper limit of normal (ULN) and aspartate aminotransferase (AST)/alanine

aminotransferase (ALT) ≤ 2.5 × ULN (see section 5.2). There is limited safety information available in

patients with total bilirubin > 1.5 × ULN and AST/ALT > 2.5 × ULN prior to dosing. Interrupt dosing

until recovery of total bilirubin to ≤ 1.5 × ULN and AST/ALT to ≤ 2.5 × ULN prior to each dose

unless due to Gilbert’s syndrome or haemolysis. Permanently discontinue treatment if total bilirubin

does not recover to ≤ 1.5 × ULN or AST/ALT does not recover to ≤ 2.5 × ULN (see Table 3 and

section 4.4).

Renal impairment

No adjustment to the starting dose is required in patients with mild, moderate, or severe renal

impairment (creatinine clearance [CL

] 60-89 mL/min, 30-59 mL/min, or 15-29 mL/min,

respectively) (see section 5.2). The safety and efficacy of BESPONSA have not been studied in

patients with end-stage renal disease.

Paediatric population

The safety and efficacy of BESPONSA in children aged 0 to <18 years have not been established. No

data are available.

Method of administration

BESPONSA is for intravenous use. The infusion must be administered over 1 hour.

BESPONSA should not be administered as an intravenous push or bolus.

BESPONSA must be reconstituted and diluted before administration. For instructions on

reconstitution and dilution of BESPONSA before administration, see section 6.6.

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Patients who have experienced prior confirmed severe or ongoing venoocclusive liver

disease/sinusoidal obstruction syndrome (VOD/SOS).

Patients with serious ongoing hepatic disease (e.g., cirrhosis, nodular regenerative hyperplasia,

active hepatitis).

Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number

of the administered product should be clearly recorded.

Hepatotoxicity, including venoocclusive liver disease/sinusoidal obstruction syndrome (VOD/SOS)

Hepatotoxicity, including severe, life-threatening, and sometimes fatal hepatic VOD/SOS, was

reported in patients with relapsed or refractory ALL receiving BESPONSA (see section 4.8).

BESPONSA significantly increased the risk of VOD/SOS above that of standard chemotherapy

regimens in this patient population. This risk was most marked in patients who underwent subsequent

HSCT.

In the following subgroups, the reported frequency of VOD/SOS post-HSCT was ≥ 50%:

Patients who received a HSCT conditioning regimen containing 2 alkylating agents;

Patients aged ≥ 65 years; and

Patients with a serum bilirubin ≥ ULN prior to HSCT.

The use of HSCT conditioning regimens containing 2 alkylating agents should be avoided. The

benefit/risk should be carefully considered before administering BESPONSA to patients in whom the

future use of HSCT conditioning regimens containing 2 alkylating agents is likely unavoidable.

In patients in whom the serum bilirubin is ≥ ULN prior to HSCT, HSCT post BESPONSA treatment

should only be undertaken after careful consideration of the benefit/risk. If these patients do proceed to

HSCT, signs and symptoms of VOD/SOS should be monitored closely (see section 4.2).

Other patient factors that appear to be associated with an increased risk of VOD/SOS after HSCT

include a prior HSCT, age ≥ 55 years, a history of liver disease and/or hepatitis before treatment, later

salvage lines, and a greater number of treatment cycles.

Careful consideration is required before administering BESPONSA to patients who have had a prior

HSCT. No patients with relapsed or refractory ALL who were treated with BESPONSA in clinical

trials had undergone HSCT within the previous 4 months.

Patients with a history of liver disease should be carefully evaluated (e.g., ultrasound scan, viral

hepatitis testing) prior to treatment with BESPONSA to exclude serious ongoing hepatic disease (see

section 4.3).

Due to the risk of VOD/SOS, for patients proceeding to HSCT, the recommended duration of

treatment with inotuzumab ozogamicin is 2 cycles; a third cycle may be considered for those patients

who do not achieve a CR or CRi and MRD negativity after 2 cycles (see section 4.2).

Signs and symptoms of VOD/SOS should be monitored closely in all patients, especially post HSCT.

Signs may include elevations in total bilirubin, hepatomegaly (which may be painful), rapid weight

gain, and ascites. Monitoring only total bilirubin may not identify all patients at risk of VOD/SOS. In

all patients, liver tests should be monitored, including, ALT, AST, total bilirubin, and alkaline

phosphatase, prior to and following each dose of BESPONSA. For patients who develop abnormal

liver tests, liver tests and clinical signs and symptoms of hepatotoxicity should be monitored more

frequently. For patients who proceed to HSCT, liver tests should be monitored closely during the first

month post-HSCT, then less frequently thereafter, according to standard medical practice. Elevation of

liver tests may require dosing interruption, dose reduction, or permanent discontinuation of

BESPONSA (see section 4.2).

Treatment should be permanently discontinued if VOD/SOS occurs (see section 4.2). If severe

VOD/SOS occurs, the patient should be treated according to standard medical practice.

Myelosuppression/cytopenias

In patients receiving inotuzumab ozogamicin, neutropenia, thrombocytopenia, anaemia, leukopenia,

febrile neutropenia, lymphopenia, and pancytopenia, some of which were life-threatening, have been

reported (see section 4.8).

In patients receiving inotuzumab ozogamicin, complications associated with neutropenia and

thrombocytopenia (including infections and bleeding/haemorrhagic events, respectively) were

reported in some patients (see section 4.8).

Complete blood counts should be monitored prior to each dose of BESPONSA and signs and

symptoms of infection during treatment and after HSCT (see section 5.1), bleeding/haemorrhage, and

other effects of myelosuppression should be monitored during treatment. As appropriate, prophylactic

anti-infectives should be administered and surveillance testing should be employed during and after

treatment.

Management of severe infection, bleeding/haemorrhage and other effects of myelosuppression,

including severe neutropenia or thrombocytopenia, may require a dosing interruption, dose reduction,

or discontinuation of treatment (see section 4.2).

Infusion related reactions

In patients receiving inotuzumab ozogamicin, infusion related reactions were reported (see

section 4.8).

Pre-medication with a corticosteroid, antipyretic, and antihistamine is recommended prior to dosing

(see section 4.2).

Patients should be monitored closely during and for at least 1 hour after the end of infusion for the

potential onset of infusion related reactions, including symptoms such as hypotension, hot flush, or

breathing problems. If an infusion related reaction occurs, the infusion should be interrupted and

appropriate medical management should be instituted. Depending on the severity of the infusion

related reaction, discontinuation of the infusion or administration of steroids and antihistamines should

be considered (see section 4.2). For severe or life-threatening infusion reactions, treatment should be

permanently discontinued (see section 4.2).

Tumour lysis syndrome (TLS)

In patients receiving inotuzumab ozogamicin, TLS, which may be life-threatening or fatal, was

reported (see section 4.8).

Pre-medication to reduce uric acid levels and hydration is recommended prior to dosing for patients

with a high tumour burden (see section 4.2).

Patients should be monitored for signs and symptoms of TLS and treated according to standard

medical practice.

QT interval prolongation

In patients receiving inotuzumab ozogamicin, QT interval prolongation was observed (see sections 4.8

and 5.2).

BESPONSA should be administered with caution in patients who have a history of, or predisposition

to QT interval prolongation, who are taking medicinal products that are known to prolong QT interval

(see section 4.5) and in patients with electrolyte disturbances. ECG and electrolytes should be obtained

prior to the start of treatment and periodically monitored during treatment (see sections 4.8 and 5.2).

Increased amylase and lipase

In patients receiving inotuzumab ozogamicin, increases in amylase and lipase have been reported (see

section 4.8).

Patients should be monitored for increases in amylase and lipase. Potential hepatobiliary disease

should be evaluated and treated according to standard medical practice.

Immunisations

The safety of immunisation with live viral vaccines during or following BESPONSA therapy has not

been studied. Vaccination with live viral vaccines is not recommended for at least 2 weeks prior to the

start of BESPONSA treatment, during treatment, and until recovery of B lymphocytes following the

last treatment cycle.

Excipients

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per 1 mg inotuzumab ozogamicin.

Patients on low sodium diets can be informed that this medicinal product is essentially ‘sodium-free’.

This medicinal product may be further prepared for administration with sodium-containing solutions

(see sections 4.2 and 6.6) and this should be considered in relation to the total sodium from all sources

that will be administered to the patient.

Interaction with other medicinal products and other forms of interaction

No formal clinical drug interaction studies have been performed (see section 5.2).

Based on in vitro data, coadministration of inotuzumab ozogamicin with inhibitors or inducers of

cytochrome P450 (CYP) or uridine diphosphate-glucuronosyltransferase (UGT) drug metabolising

enzymes are unlikely to alter exposure to N-acetyl-gamma-calicheamicin dimethylhydrazide. In

addition, inotuzumab ozogamicin and N-acetyl-gamma-calicheamicin dimethylhydrazide are unlikely

to alter the exposure of substrates of CYP enzymes, and N-acetyl-gamma-calicheamicin

dimethylhydrazide is unlikely to alter the exposure of substrates of UGT enzymes or major drug

transporters.

In patients receiving inotuzumab ozogamicin, prolonged QT interval was observed (see section 4.4).

Therefore, the concomitant use of inotuzumab ozogamicin with medicinal products known to prolong

QT interval or to induce Torsades de Pointes should be carefully considered. The QT interval should

be monitored in case of combinations of such medicinal products (see sections 4.4, 4.8, and 5.2).

Fertility, pregnancy and lactation

Women of childbearing potential/Contraception in males and females

Women of childbearing potential should avoid becoming pregnant while receiving BESPONSA.

Women should use effective contraception during treatment with BESPONSA and for at least

8 months after the last dose. Men with female partners of childbearing potential should use effective

contraception during treatment with BESPONSA and for at least 5 months after the last dose.

Pregnancy

There are no data in pregnant women using inotuzumab ozogamicin. Based on non-clinical safety

findings, inotuzumab ozogamicin can cause embryo-foetal harm when administered to a pregnant

woman. Studies in animals have shown reproductive toxicity (see section 5.3).

BESPONSA must not be used during pregnancy unless the potential benefit to the mother outweighs

the potential risks to the foetus. Pregnant women, or patients becoming pregnant while receiving

inotuzumab ozogamicin, or treated male patients as partners of pregnant women, must be apprised of

the potential hazard to the fetus.

Breast-feeding

There are no data on the presence of inotuzumab ozogamicin or its metabolites in human milk, the

effects on the breast-fed child, or the effects on milk production. Because of the potential for adverse

reactions in breast-fed children, women must not breast-feed during treatment with BESPONSA and

for at least 2 months after the final dose (see section 5.3).

Fertility

Based on non-clinical findings, male and female fertility may be compromised by treatment with

inotuzumab ozogamicin (see section 5.3). There is no information on fertility in patients. Both men

and women must seek advice for fertility preservation before treatment.

Effects on ability to drive and use machines

BESPONSA has moderate influence on the ability to drive and use machines. Patients may experience

fatigue during treatment with BESPONSA (see section 4.8). Therefore, caution is recommended when

driving or operating machines.

Undesirable effects

Summary of the safety profile

The most common (≥ 20%) adverse reactions were thrombocytopenia (51%), neutropenia (49%),

infection (48%), anaemia (36%), leukopenia (35%), fatigue (35%), haemorrhage (33%), pyrexia

(32%), nausea (31%), headache (28%), febrile neutropenia (26%), increased transaminases (26%),

abdominal pain (23%), increased gamma-glutamyltransferase (21%), and hyperbilirubinaemia (21%).

In patients who received BESPONSA, the most common (≥ 2%) serious adverse reactions were

infection (23%), febrile neutropenia (11%), haemorrhage (5%), abdominal pain (3%), pyrexia (3%),

VOD/SOS (2%), and fatigue (2%).

Tabulated list of adverse reactions

Table 5 shows the adverse reactions reported in patients with relapsed or refractory ALL who received

BESPONSA.

The adverse reactions are presented by system organ class (SOC) and frequency categories, defined

using the following convention: very common ( 1/10), common ( 1/100 to < 1/10), uncommon

( 1/1,000 to < 1/100), rare ( 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be

estimated from the available data). Within each frequency grouping, adverse reactions are presented in

order of decreasing seriousness.

Table 5.

Adverse reactions reported in patients with relapsed or refractory B-cell precursor

ALL who received BESPONSA

MedDRA System organ class

Very common

Common

Infections and infestations

Infection (48%)

(includes Sepsis

and Bacteraemia [17%],

Fungal infection [9%],

Lower respiratory tract infection

[12%)], Upper respiratory tract

infection [12%], Bacterial

infection [1%], Viral infection

[7%], Gastrointestinal infection

[4%], Skin infection [4%])

Blood and lymphatic system

disorders

Febrile neutropenia (26%)

Neutropenia (49%)

Thrombocytopenia (51%)

Leukopenia (35%)

Lymphopenia

(18%)

Anaemia (36%)

Pancytopenia

(2%)

Immune system disorders

Hypersensitivity (1%)

Metabolism and nutrition

disorders

Decreased appetite (12%)

Tumour lysis syndrome (2%)

Hyperuricaemia (4%)

Nervous system disorders

Headache (28%)

Vascular disorders

Haemorrhage

(33%) (includes

Central nervous system

haemorrhage [1%], Upper

gastrointestinal haemorrhage

[6%], Lower gastrointestinal

haemorrhage [4%], Epistaxis

[15%])

Gastrointestinal disorders

Abdominal pain (23%)

Vomiting (15%)

Diarrhoea (17%)

Nausea (31%)

Stomatitis (13%)

Constipation (17%)

Ascites (4%)

Abdominal distension (6%)

Hepatobiliary disorders

Hyperbilirubinaemia (21%)

Increased transaminases

(26%)

Increased GGT (21%)

Venoocclusive liver disease

(sinusoidal obstruction

syndrome) (3% [pre-HSCT]

General disorders and

administration site conditions

Pyrexia (32%)

Fatigue (35%)

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EMA/269417/2017

EMEA/H/C/004119

EPAR summary for the public

Besponsa

inotuzumab ozogamicin

This is a summary of the European public assessment report (EPAR) for Besponsa. It explains how the

Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is

not intended to provide practical advice on how to use Besponsa.

For practical information about using Besponsa, patients should read the package leaflet or contact

their doctor or pharmacist.

What is Besponsa and what is it used for?

Besponsa is a cancer medicine used to treat a type of blood cancer which affects B cells (a type of

white blood cells) called B-cell precursor acute lymphoblastic leukaemia (ALL). Besponsa is used on its

own in adults whose cancer has come back or did not respond to previous treatment.

Besponsa is only used in patients with ‘CD22-positive B-cell precursor ALL’. This means that patients’

have a particular protein (CD22) on the surface of their white blood cells. In patients who have a type

of chromosome known as Philadelphia-chromosome, treatment with a cancer medicine called a

tyrosine kinase inhibitor should have been tried before starting Besponsa.

Because the number of patients with B-cell precursor ALL is low, the disease is considered ‘rare’, and

Besponsa was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 7 June 2013.

Besponsa contains the active substance inotuzumab ozogamicin.

How is Besponsa used?

Besponsa is given as an infusion (drip) into a vein lasting for at least one hour. The infusions are given

on days 1, 8 and 15 of a 3 or 4 week treatment cycle. The doctor may interrupt treatment or reduce

the dose, if the patient develops certain serious side effects.

Besponsa

EMA/269417/2017

Page 2/3

Patients in whom Besponsa works well should receive 2 or 3 cycles, after which they can have a stem

cell transplant to replace their bone marrow, the only curative treatment. Patients whose treatment

works well, but who are not going to receive a stem cell transplant, may receive up to a maximum of

6 cycles of treatment. In patients who do not respond to treatment, Besponsa should be stopped after

3 cycles.

Besponsa can only be obtained with a prescription, and treatment should be given under the

supervision of a doctor who has experience in the use of cancer treatments.

For further information, see the package leaflet.

How does Besponsa work?

The active substance in Besponsa, inotuzumab ozogamicin, is a monoclonal antibody (a type of

protein) that has been linked to a small molecule, N-acetyl-gamma-calicheamicin dimethylhydrazide.

The monoclonal antibody has been designed to recognise and attach to CD22 on the cancerous B cells.

Once attached, the medicine is taken up by the cell where calicheamicin becomes active, causing

breaks in the cell’s DNA and thereby killing the cancer cell.

What benefits of Besponsa have been shown in studies?

Besponsa was shown to be more effective than other chemotherapy (medicines to treat cancer) in one

main study involving 326 adults with CD22-positive B-cell precursor ALL, which had come back or had

not responded to previous treatment. The main measure of effectiveness was response to treatment.

Patients were considered to have responded if they had no remaining cancerous B cells in their blood

and bone marrow after treatment.

An analysis of the first 218 patients treated showed that after at least 2 cycles of treatment, 81% (88

out of 109) of patients receiving Besponsa responded to treatment compared with 29% (32 out of 109)

of patients receiving other chemotherapy. Patients who responded to treatment could proceed to have

a stem cell transplant.

What are the risks associated with Besponsa?

The most common side effects with Besponsa (which may affect more than 1 in 5 people) are

thrombocytopenia (low blood platelet counts), neutropenia and leucopenia (low white blood cell

counts), infection, anaemia (low red blood cell counts), tiredness, haemorrhage (bleeding), fever,

nausea (feeling sick), headache, febrile neutropenia (low white cell count with fever), abdominal pain

(stomach ache), increased levels of liver enzymes called transaminases and gamma-

glutamyltransferase, and hyperbilirubinaemia (high blood levels of bilirubin, a breakdown product of

red blood cells).

The most serious side effects are infection, febrile neutropenia, haemorrhage, abdominal pain, fever,

tiredness and veno-occlusive liver disease/sinusoidal obstruction syndrome (VOD/SOS, a serious liver

disease).

Besponsa must not be used in patients who have VOD/SOS or have had severe VOD/SOS or have

other serious liver diseases.

For the full list of all side effects and restrictions reported with Besponsa, see the package leaflet.

Besponsa

EMA/269417/2017

Page 3/3

Why is Besponsa approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) decided that Besponsa’s

benefits are greater than its risks and recommended that it be approved for use in the EU.

The CHMP considered that although there have been recent advances in the treatment of B-cell

precursor ALL, treatment options for patients remain limited. The main study showed that Besponsa

was better than other commonly used chemotherapy medicines at inducing a response in patients and

allowing them to have a curative stem cell transplant.

With regard to safety, the side effects with Besponsa are similar to those of other chemotherapy

medicines and can usually be managed by dose reduction or treatment interruption.

What measures are being taken to ensure the safe and effective use of

Besponsa?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe

and effective use of Besponsa have been included in the summary of product characteristics and the

package leaflet.

Other information aboutBesponsa

The European Commission granted a marketing authorisation valid throughout the European Union for

Besponsa on 29 June 2017.

The full EPAR for Besponsa can be found on the Agency’s website: ema.europa.eu/Find

medicine/Human medicines/European public assessment reports. For more information about

treatment with Besponsa, read the package leaflet (also part of the EPAR) or contact your doctor or

pharmacist.

The summary of the opinion of the Committee for Orphan Medicinal Products for Besponsa can be

found on the Agency’s website: ema.europa.eu/Find medicine/Human medicines/Rare disease

designation.

This summary was last updated in 06-2017.

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