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Selinexor (Xpovio®) Horizons Infosheet Clinical Trials and Novel Drugs

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Selinexor (Xpovio®) Horizons Infosheet Clinical Trials and Novel Drugs Selinexor (Xpovio®) Horizons Infosheet Clinical trials and novel drugs This Horizons Infosheet contains information on selinexor, a drug being investigated for the treatment of myeloma. The Horizons Infosheet series What is selinexor? provides information relating Selinexor is the first in a new to novel drugs and treatment family of drugs known as Selective strategies that are currently being Inhibitor of Nuclear Export (SINE™) investigated for the treatment of compounds. Selinexor works by myeloma. The series also aims to blocking the action of a protein highlight the considerable amount called XPO1 within the nucleus of research currently taking place in (centre compartment) of myeloma the field of myeloma. cells. The drugs and novel strategies described in the Horizons Infosheets What is XPO1? may not be licensed and/or XPO1 (also known as Exportin 1) approved for use in myeloma. You is a protein responsible for moving may, however, be able to access other proteins between different them as part of a clinical trial. parts of the cell. Infoline: 0800 980 3332 1 Cells are made up of two the nucleus and into the cytoplasm. compartments called the cytoplasm The tumour suppressor proteins and the nucleus, which are separated are then activated as normal within by a plasma membrane. Some the nucleus of the myeloma cell, proteins involved in the life cycle of leading to controlled death of the the cell, for example so-called tumour myeloma cells. suppressor proteins, are active only when located within the nucleus. How is selinexor given? Other proteins must be moved from Selinexor is given in tablet form. the nucleus into the cytoplasm to It can be given on its own as a become active. The compartment in monotherapy but it has shown to which different proteins are located be most effective when used in can therefore affect the growth and combination with other myeloma survival of the cell. treatments such as dexamethasone. XPO1 is a transport protein The dose of selinexor may be 80mg responsible for moving proteins twice a week or 100mg once a week. out of the nucleus of a cell into the cytoplasm. One of the What evidence exists to support characteristics of myeloma cells the use of selinexor? that makes them different from healthy cells is their high level of In the large-scale BOSTON trial, XPO1, which has been found to be selinexor combined with bortezomib essential for myeloma cell survival. and dexamethasone (SVd) was Myeloma cells use XPO1 to move compared with bortezomib and tumour suppressor proteins from dexamethasone alone (Vd). 402 the nucleus into the cytoplasm. patients were included in the trial, of This deactivates them and allows whom half were given SVd weekly, the myeloma cells to multiply and the other half were given Vd uninhibited. twice weekly. The patients had relapsed and refractory myeloma, How does selinexor work? with between one and three previous treatment lines. In the Selinexor is the first myeloma drug SVd group, the average time before developed to block the action of the myeloma came back (called XPO1. By blocking XPO1, selinexor progression-free survival) was prevents myeloma cells from moving significantly longer than in the Vd tumour suppressor proteins out of group (14 months compared with 2 myeloma.org.uk 9.5 months). Overall response rate In a number of patients in trials, side was also significantly higher in the effects have been severe enough to SVd group than in the Vd group require reduction of the drug dose (76% of the SVd group versus 62% or stopping treatment. Because of the Vd group). selinexor is not yet in widespread use, new side effects may emerge This trial supports the results of which have not yet been reported. earlier smaller-scale trials, which indicated that selinexor could be effective in patients who are Is selinexor currently available relapsed and/or refractory to other in any UK clinical trials? treatments, and that selinexor is Most selinexor clinical trials are more effective in combination with being done in patients who have had other drugs than on its own. multiple relapses and treatments, and for whom existing treatment What are the possible known side options are limited, rather than effects of selinexor? patients at earlier stages of their treatment pathway. Selinexor is a new treatment which can cause serious side effects. Side For an up-to-date list of UK clinical effects which have been reported so trials involving selinexor, visit the far include: Myeloma Trial Finder on myeloma.org.uk • Effects on the blood: low platelet counts and bleeding; anaemia; To be enrolled on a clinical trial, low white cell counts and patients have to meet certain infections; and reduced sodium conditions known as eligibility or phosphate in the blood criteria. You should speak to your doctor in the first instance if you are Digestive effects: nausea, • interested in taking part in a trial. vomiting, diarrhoea, loss of appetite and weight loss If you are considering taking part in a clinical trial your doctor will discuss Fatigue • in detail the risks and benefits for • Cataracts (developing or new) you. They will give you detailed information to enable you to make an informed decision about whether to take part. Infoline: 0800 980 3332 3 Availability of selinexor Scotland’s drug appraisal body is in the UK the Scottish Medicines Consortium (SMC). Selinexor is not currently available for use in myeloma in the UK, and is only accessible to patients as part For more information see the Health of a clinical trial, or as part of an Technology Assessment (HTA) expanded access programme which Infosheet from Myeloma UK the manufacturer has put in place. Before a drug can be widely used, it Future directions must first be licensed as a safe and Selinexor continues to be studied effective treatment. This is usually in combination with steroids and done by the regulatory authorities various other anti-myeloma drugs. at a European level and involves a These trials will combine to provide review of evidence from large-scale better information about the best clinical studies. way to use selinexor in myeloma. Normally, the licensed drug must A trial developed with then be approved by a UK drug Myeloma UK started in 2018. appraisal body before it can be It is looking at the combination routinely prescribed by NHS doctors. of selinexor, cyclophosphamide The drug appraisal process differs and prednisolone, compared from licensing – it looks at how with cyclophosphamide and effective the newly-licensed drug prednisolone alone, in patients who is compared with existing drugs have relapsed after two or more already in use on the NHS, and previous drug treatments. decides whether the drug offers the NHS good value for money. In December 2020, the US Food and Drug Administration (FDA) approved The main body responsible for selinexor for use in combination with carrying out drug appraisals bortezomib and dexamethasone, in England and Wales is the in myeloma patients who have had National Institute for Health and one or more previous treatments. Care Excellence (NICE). NICE This approval was based on the recommendations are usually results of the BOSTON trial. The adopted in Northern Ireland. FDA previously approved selinexor 4 myeloma.org.uk with dexamethasone in 2019, for • Selinexor is not yet widely myeloma patients after multiple available in the UK, because it has relapses. not been licensed and approved for use in myeloma. However, Summary patients may be treated with it as part of a clinical trial or an Selinexor is a new drug that • expanded access programme is being investigated for the treatment of myeloma About this Infosheet Selinexor is the first in a new • The information in this Infosheet class of drugs called SINETM is not meant to replace the advice compounds. It works by blocking of your medical team. They are the the movement of particular people to ask if you have questions proteins within cells. The aim is about your individual situation. to use this to stop myeloma cells from multiplying out of control For a list of references used to develop our resources, visit Clinical trials with selinexor have • myeloma.org.uk/references so far been promising, indicating that selinexor in combination We value your feedback about our with other drugs is a potential patient information. treatment option in patients For a short online survey go to with relapsed and refractory myeloma.org.uk/pifeedback myeloma. Trials are continuing to or email comments to provide further information about [email protected] selinexor’s effectiveness and side effects, and to compare it with existing myeloma treatments • Selinexor can cause serious side effects, which have so far included effects on blood cell counts, digestive effects, and fatigue Infoline: 0800 980 3332 5 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 6 myeloma.org.uk Notes Infoline: 0800 980 3332 7 Horizons Infosheet – Clinical trials and novel drugs: Selinexor 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 Trusted Information Creator Myeloma UK 22 Logie Mill, Beaverbank Business Park, Edinburgh EH7 4HG Published by: Myeloma UK 0131 557 3332 Publication date: November 2016 Last updated: January 2021 [email protected] Review date: July 2021 Registered Charity No: SC026116 Myeloma Awareness Week • 21–27 June.
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