Belantamab mafodotin (Blenrep®) Horizons Infosheet Clinical trials and novel drugs

This Horizons Infosheet contains information on belantamab mafodotin (Blenrep®), a drug being investigated for the treatment of myeloma. The Horizons Infosheet series What is belantamab provides information relating mafodotin? to novel drugs and treatment Belantamab mafodotin is a new drug strategies that are currently being being investigated for the treatment investigated for the treatment of of myeloma. It is a type of drug known myeloma. The series also aims to as an antibody-drug conjugate. highlight the considerable amount of research currently taking place in What are antibody- the field of myeloma. drug conjugates? The drugs and treatment strategies Antibody-drug conjugates consist of described in the Horizons Infosheets two parts joined together: may not be licensed and/or approved for use in myeloma. You • A monoclonal antibody may, however, be able to access • A chemotherapy drug (a drug them as part of a clinical trial. intended to kill cancer cells)

Infoline: 0800 980 3332 1 What is a monoclonal How do antibody-drug antibody? conjugates work? Monoclonal antibodies are made Antibody-drug conjugates work in in the laboratory to mimic the two main ways. antibodies that your own immune Firstly, antibody-drug conjugates system produces in response to act as a “delivery system” for a foreign organisms (such as bacteria) chemotherapy drug. The monoclonal or abnormal cells. Antibodies antibody part recognises and recognise proteins on the surface of attaches to a specific protein on a harmful or abnormal cells and flag cell. The chemotherapy drug linked them for destruction by the immune to the antibody can then enter that system. cell directly. Monoclonal antibodies are As well as delivering the designed to recognise and attach chemotherapy, the monoclonal to specific proteins on the surface antibody in the antibody-drug of abnormal cells such as myeloma conjugate flags the cell for the cells. ‘Monoclonal’ means all one body’s immune system to destroy. type. This means that each group of monoclonal antibodies is made The way antibody-drug conjugates up of identical copies of one type work is shown in Figure 1. of antibody and recognises one particular protein. How does belantamab Monoclonal antibody drugs can mafodotin work? be used to treat cancers including The monoclonal antibody myeloma, for example daratumumab (belantamab) recognises a protein (Darzalex®) is a monoclonal on the surface of myeloma cells antibody drug licensed for treatment called BCMA. Myeloma cells have a of myeloma. Monoclonal antibodies lot of BCMA on their surface, while also form part of antibody-drug healthy cells have very little. This conjugates. means that the belantamab can effectively target myeloma cells, For more information see the and the effects on healthy cells are Immunotherapy Horizons Infosheet minimised. from Myeloma UK

2 myeloma.org.uk 1. Monoclonal antibody part of the conjugate locks onto Surface proteins a cell surface protein

Antibody-drug conjugate

Monoclonal 2. Antibody-drug conjugate antibody is absorbed into the cell Chemotherapy drug

Myeloma cell

Monoclonal antibodies on the surface of the myeloma cell trigger an immune response

3. The antibody-drug conjugate is broken down 4. Chemotherapy drug is released and kills the cell

Figure 1. Mechanism of action of antibody-drug conjugates in myeloma

The chemotherapy drug linked to absorbed into the myeloma cell, and the belantamab is called mafodotin. the mafodotin is then released and It works by stopping normal cell acts to kill the cell. processes in actively dividing cells The belantamab attached to the and causing cell death. Mafodotin is BCMA on the cell surface also too toxic to be given on its own – the triggers an immune response linker attaching it to the belantamab against the myeloma cells. stops it being released in the body until it is inside a myeloma cell. How is belantamab Once the belantamab has mafodotin given? recognised the BCMA on the surface Belantamab mafodotin is given as of a myeloma cell and attached an intravenous infusion (into the to it, the belantamab mafodotin is vein). The recommended dose

Infoline: 0800 980 3332 3 is 2.5 milligrams of drug per is expected that the eye changes kilogram of body weight (2.5mg/kg), will return to normal over time, but given every three weeks. that this can take months in some cases. Patients should have their What evidence exists eyes checked before and during to support the use of belantamab mafodotin treatment. belantamab mafodotin? They should be given eye drops to protect against dry eyes. Patients An ongoing study of belantamab who have had dry eyes before may mafodotin called DREAMM-2 be at more risk of eye problems with involved 196 patients whose belantamab mafodotin. myeloma had returned after several lines of treatment and did Other side effects seen with not respond to other treatments. belantamab mafodotin include: Belantamab mafodotin 2.5mg/kg Reduced numbers of platelets in was given to 97 of the patients (the • the blood others were given a higher dose which is not now recommended). • Anaemia Nearly a third of the 97 patients Pneumonia (lung infection) or (32%) responded to the treatment • fever at the 2.5mg/kg dose, and the response lasted on average for • Infusion reactions (symptoms that 11 months. happen during or after infusion) - these are usually mild and What are the possible short-lived known side effects of • Increase in a blood enzyme called belantamab mafodotin? aspartate aminotransferase Many patients treated with Nausea belantamab mafodotin have • changes to the cornea (surface of • Diarrhoea the eye) called keratopathy. In some Because belantamab mafodotin is a cases this can cause symptoms relatively new drug, new side effects including blurred vision, dry eyes, may emerge which have not yet or reduction in how well you can been reported. see. In more severe cases the belantamab mafodotin dosage has to be reduced or delayed. It

4 myeloma.org.uk Is belantamab mafodotin from licensing. It compares how currently available in effective the newly-licensed drug any UK clinical trials? is to existing drugs already in use on the NHS and decides whether it For an up-to-date list of UK clinical offers the NHS good value for money. trials involving belantamab mafodotin, visit the Myeloma Trial The main body responsible for Finder at trials.myeloma.org.uk carrying out drug appraisals in England and Wales is the To be enrolled on a clinical trial, National Institute for Health and patients have to meet certain Care Excellence (NICE). NICE conditions known as eligibility recommendations are usually criteria. You should speak to your adopted in Northern Ireland. doctor in the first instance if you are Scotland’s drug appraisal body is interested in taking part in a trial. the Scottish Medicines Consortium If you are considering taking part in (SMC). a clinical trial your doctor will discuss Belantamab mafodotin was licensed in detail the risks and benefits for for use in the EU in August 2020. you. They will give you detailed The licence is for patients with information to enable you to make myeloma who have received at an informed decision about whether least four previous treatments and to take part. whose myeloma is refractory to several drug types. The licence is Availability of belantamab conditional, meaning that more mafodotin in the UK evidence about the drug is needed. Before a drug can be widely used, it The drug was licensed ahead of this must first be licensed as a safe and evidence, because it was believed effective treatment. This is usually to meet an unmet medical need for done by regulatory authorities at patients with advanced myeloma. a European level and involves a review of evidence from large-scale Belantamab mafodotin has not been clinical trials. appraised by any drug appraisal bodies in the UK, but patients may Normally, the licensed drug must be treated with it as part of a clinical then be approved by a UK drug trial. Some patients who are not appraisal body before it can be eligible for a clinical trial may be routinely prescribed by NHS doctors. treated with belantamab mafodotin The drug appraisal process differs as part of an expanded access

Infoline: 0800 980 3332 5 (compassionate use) programme • Belantamab mafodotin has which has been set up by the drug shown anti-myeloma effects in manufacturer. patients with relapsed and/or refractory myeloma who have Future directions received several previous lines of treatment, and further clinical A larger clinical trial is underway, trials are underway or planned which will compare belantamab mafodotin with a standard myeloma • Side effects seen so far with treatment (pomalidomide and belantamab mafodotin have dexamethasone), in patients with included effects on the surface relapsed and/or refractory myeloma. of the eye, vision loss and blurred vision, lower levels of platelets in Clinical trials are also underway the blood, and anaemia which will look at safety and effectiveness of belantamab • Belantamab mafodotin is not mafodotin given in combination with yet widely available because it other anti-myeloma drugs. has not been approved in the UK for use in myeloma. However, Key points patients may be treated with it • Belantamab mafodotin (Blenrep®) through a clinical trial is a new drug being investigated for the treatment of myeloma About this Infosheet The information in this Infosheet Belantamab mafodotin is type • is not meant to replace the advice of drug called an antibody-drug of your medical team. They are the conjugate people to ask if you have questions • The drug contains a monoclonal about your individual situation. antibody which targets proteins For a list of references used to called BCMA on myeloma cells. develop our resources, visit This is linked to a chemotherapy myeloma.org.uk/references drug We value your feedback about our The chemotherapy drug is • patient information. delivered direct to myeloma cells, For a short online survey go to and once inside them can kill myeloma.org.uk/pifeedback them or email comments to [email protected]

6 myeloma.org.uk Other information available from Myeloma UK Myeloma UK has a range of publications available covering all aspects of myeloma, its treatment and management. Download or order them from myeloma.org.uk/publications To talk to one of our Myeloma Information Specialists about any aspect of myeloma, call our Myeloma Infoline on 0800 980 3332 or 1800 937 773 from Ireland. The Infoline is open from Monday to Friday, 9am to 5pm and is free to phone from anywhere in the UK and Ireland. Information and support about myeloma is also available around the clock at myeloma.org.uk

Infoline: 0800 980 3332 7 Horizons Infosheet – Clinical trials and novel drugs: Belantamab mafodotin

We’re here for everything a diagnosis of myeloma brings Get in touch to find out more about how we can support you Call the Myeloma Infoline on 0800 980 3332 Email Ask the Nurse at [email protected] Visit our website at myeloma.org.uk

Myeloma UK 22 Logie Mill, Beaverbank Business Park, Edinburgh EH7 4HG Published by: Myeloma UK 0131 557 3332 Publication date: April 2020 Last updated: November 2020 [email protected] Review date: May 2021 Registered Charity No: SC026116

Myeloma Awareness Week • 21–27 June