Carfilzomib (Kyprolis®)
This Horizons Infosheet contains information on carfilzomib (also known as Kyprolis®), a drug being investigated for the treatment of myeloma.
The Horizons Infosheet series Horizons Infosheets may not be provides information relating licensed and/or approved for use to novel drugs and treatment in myeloma. You may, however, strategies that are currently being be able to access them as part of investigated for the treatment of a clinical trial. myeloma. The series also aims to highlight the considerable What is carfilzomib? amount of research currently Carfilzomib is a new drug being taking place in the field of used to treat myeloma. myeloma. Like bortezomib (Velcade®), The drugs and treatment carfilzomib belongs to a group strategies described in the of drugs known as proteasome
Horizons Clinical trials Infosheet and novel drugs Series Infoline: 0800 980 3332 1 Velcade
inhibitors. Carfilzomib works of proteasomes than other types in a similar way to bortezomib of cancer cells. This may be due however it has been developed to the need of the myeloma to target a different part of the cells to dispose of the abnormal proteasome. This is thought to protein (paraprotein) they make carfilzomib more effective produce. and potentially cause fewer side- By blocking the function of the effects than bortezomib. proteasome, carfilzomib prevents the myeloma cells from growing What are proteasomes? and multiplying. Proteasomes are large molecules which are present in all cells in small protein tags the body. They are involved in small protein tags the removal, breakdown and recycling of damaged proteins or those that are no longer needed by the cell. protein tagged protein tagged for recycling for recycling How does carfilzomib work? proteasome proteasome Carfilzomib works by binding to protein protein fragments proteasomes and permanently fragments blocking their function which proteasome inhibitors block the stops them from breaking down proteasome inhibitors block the proteasome causing proteins to proteasome causing proteins to build up unwanted proteins (Figure 1). build up This causes proteins to build drug up and become toxic, killing drug the cell. Myeloma cells multiply more quickly than normal healthy cells and rely more heavily on proteasomes as they produce unwanted proteins at a faster rate. Myeloma cells are therefore much more sensitive to carfilzomib than normal cells. Figure 1. Mechanism of action of proteasome Myeloma cells appear to be even inhibitors more dependent on the actions Figure: MUK10_proteasome_inhib-CMYK ©www.myeloma.org.uk design by www.blink.biz Figure: MUK10_proteasome_inhib-2COL ©www.myeloma.org.uk design by www.blink.biz
2 www.myeloma.org.uk How is carfilzomib given? treatment cycle. Carfilzomib is Carfilzomib is given as an given over 2 consecutive days intravenous (into the vein) each week for 3 weeks followed infusion. It has been shown to by 12 days off. It is administered be most effective when used in as a 10-minute infusion starting at 2 combination with other myeloma 20mg/m on days 1 and 2 of the treatments such as lenalidomide first cycle. If this dose is tolerated, 2 (Revlimid®) and dexamethasone. the dose is increased to 27mg/m for the remaining cycles. Carfilzomib and dexamethasone Patients receive lenalidomide When given in combination with each day on days 1 to 21 and dexamethasone only, carfilzomib dexamethasone on days 1, 8, 15 is administered over a 28-day and 22 of each cycle. treatment cycle. It is administered Carfilzomib is given for a as a 30-minute infusion starting maximum of 18 cycles when 2 at 20mg/m (your height and given with lenalidomide and weight will be measured to dexamethasone. find the correct dose) over 2 consecutive days each week for What evidence exists to support 3 weeks. If this dose is tolerated the use of carfilzomib? it is increased to 56mg/m2 for the remaining cycles. In the Phase III ASPIRE clinical trial, progression free survival Low-dose dexamethasone (the length of time following (20mg/m2) is given on days 1, 2, tretment before the myeloma 8, 9, 15 and 16 of a cycle. returns) increased from an Carfilzomib with dexamethasone average of 17.6 months in those is given until the myeloma shows being treated with lenalidomide signs it is beginning to become and dexamethsone to 26.3 active again. months in those being treated with carfilzomib, lenlidomide and Carfilzomib, lenalidomide and dexamethasone. dexamethasone Further evidence from the Phase When given in combination III ENDEAVOR clinical trial found with lenalidomide and that progression free survival dexamethasone, carfilzomib nearly doubled (17.6 months is administered over a 28-day compared to 9.4 months) in
Infoline: 0800 980 3332 3 patients treated with carfilzomib Carfilzomib has also been and dexamethasone compared found to cause heart problems to patients who had bortezomib or worsen pre-existing heart and dexamethasone. conditions. Therefore, patients Carfilzomib is currently being being treated with carfilzomib investigated in combination will be monitored carefully during with other myeloma treatment. treatments. For example, the Though carfilzomib is from the MUK five trial is investigating same drug family as bortezomib, the use of carfilzomib with it is thought to cause much lower cyclophosphamide and rates of peripheral neuropathy dexamethasone. Initial results (damage to the nerves that make from this trial have found an up the peripheral nervous system overall response of nearly 88% causing pain, tingling and altered (14 of 16 patients treated). sensation). In ongoing trials, carfilzomib is proving to be an effective initial Is carfilzomib currently available treatment for newly diagnosed in any UK clinical trials? myeloma patients. For an up-to-date list of UK Research into carfilzomib as a clinical trials involving carfilzomib, monotherapy (on its own and visit the Myeloma Trial Finder on not in combination with other www.myeloma.org.uk drugs) has found that it is not as To be enrolled on a clinical trial, effective as when it is given in patients have to meet certain combination with other drugs. conditions known as eligibility criteria. You should speak to your What are the known possible doctor in the first instance if you side-effects of carfilzomib? are interested in taking part in a The most commonly reported trial. side-effects of carfilzomib include: fatigue, low platelet UK availability of carfilzomib counts (thrombocytopenia), low Before a drug can be widely red blood cell counts (anaemia), used, it must first be licensed as nausea, difficulty breathing, a safe and effective treatment. diarrhoea and fever. This is usually done by regulatory authorities at a European level
4 www.myeloma.org.uk and involves a review of evidence dexamethasone for myeloma from large-scale clinical trials. patients at first relapse, who Normally, the licensed drug have had one previous treatment must then be approved by a that did not include bortezomib. UK drug appraisal body before The approval was dependent on it can be routinely prescribed the inclusion of a patient access by NHS doctors. The drug scheme – a way of giving a appraisal process differs from discount on the price of a drug to licensing – it compares how improve its cost-effectiveness. effective the newly-licensed NICE has not recommended drug is to existing drugs already carfilzomib for use in in use on the NHS and decides combination with lenalidomide whether it offers the NHS good and dexamethasone in relapsed value for money. The main body myeloma patients. NICE issued responsible for carrying out negative guidance for this triplet drug appraisals in England and combination because of its Wales is the National Institute uncertainty about whether it for Health and Care Excellence represented a cost-effective use (NICE). NICE recommendations of NHS resources. are usually adopted in Northern Ireland. Scotland’s drug appraisal In Scotland, the SMC has also body is the Scottish Medicines turned down carfilzomib in Consortium (SMC). combination with lenalidomide and dexamethasone for relapsed myeloma patients. This is For more information see the Health Technology Assessment (HTA) Infosheet because it felt the submission from Myeloma UK did not justify the cost of the treatment to the NHS. However, Carfilzomib has been approved in August 2017 the SMC approved by the European licensing body, carfilzomib in combination with the European Medicines Agency dexamethasone alone in relapsed (EMA) for relapsed myeloma myeloma patients. patients who have received at least one previous treatment. Future directions In June 2017, carfilzomib was Carfilzomib continues to be approved for use in England studied in different patient and Wales in combination with groups and in different treatment
Infoline: 0800 980 3332 5 combinations. These trials will provide information about the safest and most effective way to use carfilzomib in myeloma.
About this Horizons Infosheet The information in this Horizons Infosheet is not meant to replace the advice of your medical team. They are the people to ask if you have questions about your individual situation. All Myeloma UK publications are extensively reviewed by patients and healthcare professionals prior to publication. For a list of references used to develop our resources, visit www.myeloma.org.uk/ references To provide feedback about this publication, email [email protected]
6 www.myeloma.org.uk Other information available from Myeloma UK Myeloma UK has a range of Essential Guides, Infoguides and Infosheets available covering many areas of myeloma, its treatment and management. To order your free copies or to talk to one of our Myeloma Information Specialists about any aspect of myeloma, call our Myeloma UK 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 www.myeloma.org.uk
Published by: Myeloma UK Publication date: April 2013 Last updated: February 2018 Review date: August 2018
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Myeloma Infoline: 0800 980 3332 or 1800 937 773 from Ireland www.myeloma.org.uk
Myeloma Awareness Week 21 - 27 June