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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/112959/2016

EMEA/H/C/000717

EPAR summary for the public

Revlimid

lenalidomide

This is a summary of the European public assessment report (EPAR) for Revlimid. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Revlimid.

What is Revlimid?

Revlimid is a cancer medicine that contains the active substance lenalidomide. It is available as capsules (2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg and 25 mg).

What is Revlimid used for?

Revlimid is used for the treatment of multiple myeloma, myelodysplastic syndromes and mantle cell lymphoma, which are conditions affecting blood cells and bone marrow.

In multiple myeloma, a cancer of a type of white blood cells called plasma cells, Revlimid is used:

•    in combination with dexamethasone (an anti-inflammatory medicine), in adults whose disease has been treated at least once in the past;

•    for the treatment of adults with previously untreated (newly diagnosed) multiple myeloma, who are not eligible for bone marrow transplant.

In myelodysplastic syndromes, a group of bone marrow disorders that cause anaemia, Revlimid is used to manage patients in whom these lead to transfusion-dependent anaemia (low red blood cell counts severe enough to require blood transfusions). In some cases, myelodysplastic syndromes can lead to acute myeloid leukaemia (AML, a type of cancer affecting white blood cells). Revlimid is used in patients who have a genetic abnormality (called deletion 5q) and are at a lower risk of AML, and it is used when other treatments are not adequate.

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In mantle cell lymphoma, a blood cancer that affects a type of white blood cell called B lymphocytes, Revlimid is used in adults whose disease has come back after treatment, or does not respond to treatment.

Because the number of patients with these diseases is low, the diseases are considered 'rare', and Revlimid was designated an 'orphan medicine' (a medicine used in rare diseases) on 12 December 2003, 8 March 2004 and 27 October 2011.

The medicine can only be obtained with a prescription.

How is Revlimid used?

Treatment with Revlimid must be monitored by doctors who have experience in the use of cancer medicines.

Revlimid is taken in repeated 28-day cycles: the patient takes the medicine once a day for 21 days at around the same time each day, followed by seven days off the medicine.

In the treatment of patients with multiple myeloma who have received at least one prior therapy, and in the treatment of mantle cell lymphoma, the recommended dose of Revlimid is 25 mg a day.

In the treatment of newly diagnosed multiple myeloma, the recommended dose ranges between 10 and 25 mg per day, depending on the other cancer medicines the patient is taking.

In the treatment of myelodysplastic syndromes, the recommended dose of Revlimid is 10 mg a day.

The dose of Revlimid should be reduced or treatment interrupted depending on the patient's condition, the severity of any side effects and the levels of platelets (components that help the blood to clot) and of neutrophils (a type of white blood cell that helps fight infection). A lower dose should also be used in patients who have moderate or more severe problems with their kidneys. For more information, see the summary of product characteristics (also part of the EPAR).

How does Revlimid work?

The active substance in Revlimid, lenalidomide, is an immunomodulating agent. This means that it affects the activity of the immune system (the body's natural defences). Lenalidomide works in a number of different ways: it blocks the development of abnormal cells, prevents the growth of blood vessels within tumours and also stimulates some of the specialised cells of the immune system to attack the abnormal cells.

How has Revlimid been studied?

Revlimid has been studied in two main studies involving 704 patients with previously treated multiple myeloma. In both studies, Revlimid was compared with placebo (a dummy treatment), both taken in combination with dexamethasone. The main measure of effectiveness was how long it took until the disease got worse.

In newly diagnosed multiple myeloma, Revlimid has been studied in two main studies, involving a total of around 2,000 patients, which looked at how long patients lived without their disease getting worse. The first study compared Revlimid with placebo, both taken with melphalan and prednisone. The second study compared Revlimid taken with low dose dexamethasone with standard treatment.

Two main studies have also been carried out involving a total of 353 patients with lower risk myelodysplastic syndromes. The first study did not compare Revlimid with any other treatment, while

Revlimid

the second study compared it with placebo. The main measure of effectiveness was the number of patients who did not need a blood transfusion for at least 56 days in the first study and 182 days in the second study.

One main study involving 254 patients has been carried out in patients with mantle cell lymphoma that had come back after, or failed to respond to, previous treatment. Revlimid was compared with an appropriate medicine chosen by the patients' doctors, and the main measure of effectiveness was how long it took until the disease got worse.

What benefit has Revlimid shown during the studies?

Revlimid was more effective than placebo at preventing a worsening of previously treated multiple myeloma. The results of the two studies taken together showed that, on average, it took 48.3 weeks for the disease to get worse in patients taking Revlimid, compared with 20.1 weeks in those taking placebo.

In the first study of newly diagnosed multiple myeloma, patients taking Revlimid (plus melphalan and prednisone) lived longer without their disease getting worse (27.4 months) than patients in the placebo group (14.3 month). In the second study, it took 26.4 months for the disease to get worse in patients taking Revlimid plus dexamethasone, compared with 22.7 months for those on standard treatment.

In patients with lower risk myelodysplastic syndromes, 97 out of 148 patients (66%) taking 10 mg Revlimid in the first study did not need a blood transfusion for at least 56 days. In the second study,

38 out of 69 patients (55%) taking 10 mg Revlimd did not need a blood transfusion for at least 182 days, compared with 4 out of 67 (6%) taking placebo.

For patients with mantle cell lymphoma, the average time before the disease got worse was 37.6 weeks in those treated with Revlimid, compared with 22.7 weeks in those given other treatments.

What is the risk associated with Revlimid?

The most common side effects with Revlimid for the treatment of multiple myeloma are: fatigue (tiredness), neutropenia (low levels of neutrophils, a type of white blood cell), constipation, diarrhoea, muscle cramps, anaemia (low red blood cell counts), thrombocytopenia (low platelet counts), rash, back pain, insomnia, decreased appetite, cough, pyrexia (fever), peripheral oedema (swelling, specially of the ankles and feet), leucopenia (low white blood cell counts) and asthenia (weakness).The most common side effects with Revlimid for the treatment of myelodysplastic syndromes are: neutropenia, thrombocytopenia, diarrhoea, constipation, nausea (feeling sick), pruritus (itching) rash, fatigue (tiredness) and muscle spasms. The most common side effects with Revlimid for the treatment of mantle cell lymphoma are: neutropenia, anaemia, diarrhoea, fatigue, constipation, pyrexia and rash.The most serious side effects with Revlimid are: neutropenia, venous thromboembolism (problems due to the formation of blood clots in the veins) including pulmonary embolism (blood clots in the veins supplying the lungs), pneumonia (infection of the lungs), kidney failure, febrile neutropenia (neutropenia with fever), diarrhoea and anaemia. For the full list of all side effects reported with Revlimid, see the package leaflet.

Lenalidomide is expected to be harmful to the unborn child. Therefore, Revlimid must not be used in women who are pregnant. It must also not be used in women who could become pregnant, unless they take all of the necessary steps to ensure that they are not pregnant before treatment and that they do

Revlimid

EMA/112959/2016

not become pregnant during or soon after treatment. For the full list of restrictions, see the package leaflet.

Why has Revlimid been approved?

The CHMP decided that Revlimid's benefits are greater than its risks and recommended that it be given marketing authorisation.

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

A risk management plan has been developed to ensure that Revlimid is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Revlimid, including the appropriate precautions to be followed by healthcare professionals and patients.

The company that makes Revlimid will provide a letter and educational kits for healthcare workers, and brochures for patients, explaining that the medicine is expected to be harmful to the unborn child and detailing the steps that need to be taken for the medicine to be used safely. It will also supply cards for patients to ensure that all appropriate safety measures have been taken by each patient. Each Member State will also ensure that educational material and patient cards are provided to prescribers and patients.

The company has also set up a pregnancy prevention programme in each Member State and will collect information on whether the medicine is used outside its approved indication. The boxes containing Revlimid capsules also include a warning stating that lenalidomide is expected to be harmful to the unborn child.

In addition, the company will carry out a study in patients with myelodysplastic syndromes to gather further safety data, as well as a safety study in patients with newly diagnosed multiple myeloma not eligible for transplant.

Other information about Revlimid

The European Commission granted a marketing authorisation valid throughout the European Union for Revlimid on 14 June 2007.

The full EPAR for Revlimid 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 Revlimid, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

The summaries of the opinions of the Committee for Orphan Medicinal Products for Revlimid can be found on the Agency's website ema.europa.eu/Find medicine/Human medicines/Rare disease designations:

•    treatment    of multiple myeloma;

•    treatment    of mvelodvsplastic syndromes;

•    treatment    of mantle cell lymphoma.

This summary was last updated in 02-2016.

Revlimid

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