Myeloma research

All treatments have to be fully researched before they can be adopted as standard treatment for everyone. This is so that

• We can be sure they work
• We can be sure they work better than the treatments that are available at the moment
• They are known to be safe

Firstly, treatments are developed and tested in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in patients. If a treatment described here is said to be at the laboratory stage of research, it is not ready for patients and is not available either within or outside the NHS.

Tests in patients are called clinical trials. The trials and research section has information about what trials are including information about the 4 phases of clinical trials. If you are interested in taking part in a clinical trial, visit our searchable database of clinical trials. If there is a trial you are interested in, print it off and take it to your own specialist. If the trial is suitable for you, your doctor will need to make the referral to the research team. The database also has information about closed trials and trial results.

All this research is ongoing. Until studies are completed and we are certain that these new treatments really do work better than existing treatments, they cannot be used as standard treatment. If you are interested in taking part in a clinical trial, you need to ask your specialist if you may be suitable for any research studies.

There are several blood tests that can help to predict how myeloma may develop. You can ask your specialist whether they are helpful in your case. One test is called beta 2 microglobulin. A low level of this protein means that your myeloma is not very active and so is likely to develop more slowly. Another test is called serum albumin – a higher level of this protein is linked to a better outlook. There are other tests, including chromosome tests. These tests are still being researched and are not used routinely.

Doctors hope that in the future they may be able to use these tests to see which people need to start treatment quickly and when it is better to wait.

Scientists are also looking at particular abnormal genes found in myeloma cells. They may be able to use this information to find out how quickly or slowly myeloma is likely to grow in different patients. This type of information can help doctors to decide who needs the most intensive treatments.

Biological therapy is treatment with substances that occur naturally in the body or that change how cells signal to each other to grow. Biological therapies being used and tested in myeloma include

• Bortezomib (Velcade)
• Thalidomide
• Lenalidomide (Revlimid)
• Pomalidomide
• Carfilzomib
• Vaccines
• Chemical growth factors (cytokines)
• Monoclonal antibodies (MABs)
• Drugs that block cell growth

Bortezomib (Velcade)

Doctors use bortezomib (Velcade) for people with myeloma that has come back, or has continued to grow. Bortezomib is a type of biological therapy called a proteasome inhibitor. From research so far, we know that bortezomib with steroids is better at controlling myeloma that has stopped responding to chemotherapy than treatment with the steroid dexamethasone alone. Other studies have shown that people who have bortezomib alongside chemotherapy as the first treatment for myeloma can have a very good response. Myeloma disappears (complete remission) in more people who have bortezomib with chemotherapy than in people who have chemotherapy alone.

The PADIMAC trial is looking at a combination of the drugs bortezomib (Velcade), doxorubicin (Adriamycin) and dexamethasone (PAD) as a first treatment for myeloma. The aim of this trial is to see if people who have a good response to PAD can safely wait until their myeloma comes back to have a stem cell transplant.

The MMVAR trial is looking at whether adding bortezomib (Velcade) to thalidomide and dexamethasone works better for people with myeloma that has come back after having a stem cell transplant. 

Two new drugs that are similar to bortezomib are being tested in trials in some European countries and the USA – MLN 9708 and ONX 0912. These are proteasome inhibitors taken as tablets.

Thalidomide

Thalidomide is a drug that affects the chemicals cells use to signal to one another. It can affect all sorts of cell processes, including the growth of cancer cells. Thalidomide is also known as an anti angiogenic drug, which means that it stops tumours from growing new blood vessels. We already know that thalidomide can be very helpful for myeloma that has come back or has stopped responding to other types of treatment.

The MYELOMA 11 trial is comparing thalidomide to another biological therapy drug called lenalidomide when combined with the chemotherapy drug cyclophosphamide and the steroid, dexamethasone. It is for people newly diagnosed with myeloma.

Research is also currently looking at whether thalidomide is helpful as a maintenance treatment. This is a treatment that you take over a long period of time to help keep a disease under control. Early research has suggested that people who take thalidomide after high dose therapy may stay free of their myeloma for longer.

Lenalidomide (Revlimid)

Research is going on into similar drugs to thalidomide. Many researchers believe these may end up working better than thalidomide. Lenalidomide (Revlimid) has been shown to work in phase 3 clinical studies of people with myeloma.

Lenalidomide is similar to thalidomide and carries a similar risk of blood clots (deep vein thrombosis, or DVT). It also seems to have some different side effects. The most common side effects seen in results from clinical trials are a low white blood cell and platelet count. This can mean an increased risk of infections and bleeding. Research has suggested that there may be an increased risk of a second cancer after using lenalidomide for a long time. But we need more research to confirm whether this is correct.

A phase 3 trial in the UK is looking at treatment of myeloma in older people. It is comparing lenalidomide (Revlimid) and dexamethasone to one of the standard treatments (melphalan, prednisone and thalidomide). 

The LenaRIC trial is a trial funded by Cancer Research UK. It is looking at giving lenalidomide after a stem cell transplant with lower dose chemotherapy using cells from a donor. The lower dose chemotherapy transplant is called reduced intensity conditioning (RIC). The aims of this trial are to see if having lenalidomide after a reduced intensity conditioning transplant is safe and helps to stop myeloma coming back.

The UK Myeloma 11 trial is comparing lenalidomide to thalidomide. The aim of this trial is to find out how well the combination of lenalidomide, cyclophosphamide and dexamethasone works for people with myeloma.

Pomalidomide

Early trials have been looking at a new drug called pomalidomide. A phase 2 trial was reported at the 2010 American Society of Haematology meeting. It looked at pomalidomide and dexamethasone in people with myeloma who had already had bortezomib (Velcade) and lenalidomide (Revlimid) treatment. The results with pomalidomide were promising but we need larger studies to know how helpful it may be.

The NIMBUS study is a large scale international Phase 3 study comparing pomalidomide and low dose dexamethasone with high dose dexamethasone in patients with relapsed or refractory myeloma. The researchers want to find out whether people do better on pomalidomide and dexmethasone or dexamethasone alone. You can find out about the NIMBUS study on the Myeloma UK website.

Carfilzomib

Research is looking into similar drugs to bortezomib (Velcade) for myeloma. One is carfilzomib. Early studies in America have found this drug may be helpful in controlling myeloma that has come back after previous treatments. It doesn't cause the severe tingling and numbness in the fingers and toes (peripheral neuropathy) that can be a side effect of bortezomib (Velcade). 

The UK ASPIRE study is aiming to find out if carfilzomib, in combination with lenalidomide (Revlimid) and low dose dexamethasone, works better than lenalidomide and dexamethasone. This is a phase 3 study for people with myeloma that has relapsed. It has now closed but you can find information about the ASPIRE study on the Myeloma UK website. 

Vaccines

Vaccine treatment for myeloma is still highly experimental and is only available within clinical trials. As with other some forms of biological therapy, myeloma vaccines are designed to try to encourage your own immune system to pick out and attack myeloma cells. As the immune system is able to remember abnormal cells and recognise them, the idea is that your body would then be protected against the myeloma coming back in the future (a relapse).

Early trials are currently looking into DNA vaccines for myeloma. The vaccine is made from the patient's myeloma cells. In the educated donor lymphocyte (EDL) trial, a bone marrow donor has the vaccine before donating the bone marrow. The researchers hope that this will help the white blood cells to find any remaining cancer cells more easily once the patient has had the marrow. This is a pilot study. 

In the MMIFTT trial, the patient has the vaccine after high dose chemotherapy and stem cell rescue. This is a phase one trial. The researchers don't yet know if this treatment will work.

Chemical growth factors (cytokines)

Cells produce a number of chemical growth factors. Scientists call these chemicals cytokines (pronounced sigh-toe-kines). Cells called stromal cells, found in the tissues that support the bone marrow, make a number of these growth factors. They include substances called interleukin-6 (IL-6), IGF-1, and tumour necrosis factor (TNF alpha). IL-6 stimulates the myeloma cells to make another growth factor called VEGF. Myeloma cells need all these chemicals to grow. IL-6 also plays a part in the destruction of bone by myeloma cells. Research is under way to try and find ways to block these growth factors because that may help to stop the growth of myeloma cells.

Monoclonal antibodies

Monoclonal antibodies (MABs) are drugs that target particular proteins on cancer cells. Siltuximab is a type of monoclonal antibody. It is also called CNTO 328. It blocks the protein called interleukin-6 (IL-6), which may help cancers to grow. If your myeloma does not respond to treatment, or has come back after previous treatment, you may have bortezomib treatment. A trial is looking at whether combining siltuximab with bortezomib works better against myeloma than bortezomib (Velcade) on its own. The trial also aims to find out about the side effects of siltuximab. 

Doctors are looking at a new monoclonal antibody called BHQ880 for myeloma in people with poor kidney function. The drug works by blocking a protein called DKK1. This protein stops cells called osteoblasts from forming new bone. This often happens with myeloma and causes bone damage and pain. Blocking the DKK1 protein may allow the osteoblasts to start making new bone again.

Another monoclonal antibody doctors are researching is elotuzumab. The Eloquent 1 trial is looking at giving the drug lenalidomide (Revlimid) and the steroid dexamethasone with and without elotuzumab. The trial team want to find out if adding elotuzumab makes the treatment work better.

Drugs that block cell growth

Doctors are using a new type of biological therapy called panobinostat. Panobinostat is also known as LBH589 and it aims to stop cancer growing by blocking enzymes called deacetylases (pronounced dee-as-et-isle-azes). It is a type of deacetylase inhibitor. Cells need these enzymes to grow and divide. Blocking them may stop cancer growing. A trial is looking at panobinostat in combination with bortezomib and the steroid dexamethasone for myeloma that has come back or stopped responding to treatment. The aim of this trial is to see if adding panobinostat to bortezomib and dexamethasone helps this group of people. And the trial wants to learn more about the side effects of this drug combination.

Another deacetylase inhibitor being researched is vorinostat. It is also called Zolina. A phase 3 clinical trial is looking at giving vorinostat with bortezomib (Velade). The researchers want to find out how well these drugs work together in people who have had a stem cell transplant.

Perifosine is a drug that works by blocking the signalling pathways needed to keep cells alive. It is also called KRX-0401. Researchers in the USA are looking at how well it works in people with multiple myeloma that is not responding to treatment or has come back after previous treatment. Perifosine is in phase 3 clinical trials in the USA.

Bendamustine is a chemotherapy drug that has been used for many years for blood cancers. The MUK One trial is for people whose myeloma has come back or is not responding to treatment. It is trying to find out the best dose of bendamustine when it is given in combination with thalidomide and dexamethasone. The study is comparing two different doses of treatment.

Doxorubicin is a chemotherapy drug which is often used to treat myeloma. There is a newer form of doxorubicin called Caelyx (liposomal doxorubicin). Liposomal means that the chemotherapy is held in a fatty covering. This allows it to stay in your blood for longer, and protects healthy cells, so that the chemotherapy causes fewer side effects. Caelyx may sometimes be used with bortezomib (Velcade) to treat myeloma which has progressed or come back. It is for people who have already had at least one treatment, and has had, or is not suitable for, a bone marrow or stem cell transplant. 

The ADMYRE trial is looking at a new type of chemotherapy called plitidepsin with dexamethasone for myeloma that has come back or is not responding to treatment. Plitidepsin is also known as Aplidin and it also works like a biological therapy to stop the myeloma making new blood vessels. The study aims to see if plitidepsin and dexamethasone help people with relapsed or refractory myeloma more than dexamethasone alone. It also wants to learn more about the side effects.

You can find out about chemotherapy trials for myeloma on our clinical trials database. Choose 'myeloma' from the dropdown menu of cancer types. If you want to see all the trials, tick the boxes for closed trials and trial results.

Bisphosphonates are drugs that can help to slow the breakdown of bone. They can reduce the risk of a bone breaking and can also reduce pain in people with myeloma. 

In a phase 3 trial called Myeloma IX researchers compared two types of bisphosphonates. They looked at injections of zoledronic acid and  clodronate tablets. Everyone in the trial had chemotherapy. The researchers found that people who had zoledronic acid and chemotherapy lived longer and were less likely to have bone problems. A side effect of bisphosphonates is osteonecrosis of the jaw. People taking the zoledronic acid were more likely to develop this effect but it was still rare. 4 out of every 100 people (4%) having zoledronic acid developed osteonecrosis compared to less than 1 in 100 people taking clodronate.

Platelet transfusions are often given during treatment for myeloma – to prevent bleeding. Chemotherapy can slow the production of platelets by the bone marrow so there are less in the blood. If the level of platelets gets very low, you may bruise easily, have nosebleeds or bleed more, or longer, than usual from cuts or grazes. Doctors check your level of platelets and, if they are very low, you normally have platelets through a drip.

Doctors don't really know if these platelet transfusions are needed to prevent bleeding. There are small risks associated with platelet transfusions. Some people have a reaction to the platelets and sometimes this can be serious. Also, there is a small risk of getting an infection from transfusions.

The TOPPS trial is finding out whether it is safe to wait until you have early signs of bleeding, such as bleeding gums, before having a platelet transfusion. The researchers want to find out if platelet transfusions are really needed for people who have a low platelet count, but no signs of bleeding. The aim is to compare the different ways of using platelet transfusions. This may affect the way doctors use them in the future.

Intensive treatment with high dose chemotherapy followed by stem cell rescue or bone marrow transplant, has been used to treat myeloma for some time. Doctors are continuing to try to improve the results of this type of treatment. It is already getting safer. A few years ago, it wasn't really an option for anyone over 45 because the side effects were too severe. Now doctors are willing to use it for fit patients up to 70 because there are better ways of controlling the side effects. 

The doctors researching this treatment also want to lengthen the time that it can keep myeloma in remission. They hope that they may eventually be able to cure it. The latest developments are

• Double transplant
• Mini transplant
• Treatment for sore mouth
• Plerixafor
• Timing of transplant

Double transplant

Double transplants are also called tandem transplants. This means having another stem cell or bone marrow transplant about 6 months after the first. It is usually another transplant using your own stem cells. This approach may help to keep the myeloma in remission for longer. But having two transplants increases the risks and side effects, so doctors are continuing to research this.

Researchers are also looking into giving a second transplant when myeloma comes back. This is not the same as tandem transplant, which is planned and done before relapse happens. There is a trial which you may be able to join if you had your stem cell transplant at least 18 months ago, and your myeloma has now come back and is causing symptoms. This is called the Myeloma X Relapse - Intensive trial. Everyone on this trial first has treatment with bortezomib, doxorubicin and dexamethasone. This is called the PAD combination. 

People in the trial have between 2 and 4 cycles of PAD treatment, depending on how well it works. Then one group of patients has a second transplant of their own stem cells. The other group of patients has low dose chemotherapy with cyclophosphamide tablets. The doctors want to find out which one of these treatments controls the myeloma for longer, and how well PAD treatment works for people with relapsed myeloma. 

Mini transplant

Doctors call these transplants reduced intensity conditioning (RIC) allografts. Conditioning means the chemotherapy or radiotherapy treatment you have as part of your transplant. Allograft (or allogeneic) means a transplant from another person. A mini transplant means you have less intensive treatment than you would as part of a standard donor bone marrow or stem cell transplant. So you have chemotherapy, but not enough to destroy your bone marrow completely. It is enough to stop you reacting to bone marrow or stem cells from a matched donor. A matched donor is a donor whose bone marrow matches yours, and is usually a brother or sister. The aim of this type of transplant is to get the best chance of a long remission by using stem cells or bone marrow from another person to treat your myeloma. But allografts have more risks and side effects than a transplant using your own cells. So they are not suitable for everyone.

At the moment allografts are usually only offered as part of a clinical trial. If you have a suitable donor and are offered this treatment, your specialist may suggest that you have chemotherapy to get the myeloma under control, followed by intensive chemotherapy and a stem cell transplant using your own stem cells. Then a mini donor transplant. 

If your myeloma does not respond, or comes back after the transplant, your doctor might suggest treatment with white blood cells (lymphocytes) from your donor. Doctors call this donor lymphocyte infusion or DLI.

Treatment for sore mouth

If you are having a stem cell transplant, you will probably have high dose melphalan chemotherapy. Melphalan can make your mouth very sore, making it difficult to eat and drink. There is a trial of a drug called palifermin, which makes the cells in your mouth and throat grow back quicker after chemotherapy. Doctors want to see how well palifermin works if it is only given before your transplant. They also want to find out if it causes or worsens cataracts (clouding over of the lens in the eye). 

Plerixafor (Mozobil) 

Plerixafor (Mozobil) works by helping your bone marrow to release stem cells into your bloodstream. The stem cells are then collected to use for a stem cell transplant. Plerixafor is used in combination with G-CSF. A phase 2 trial called PHANTASTIC is comparing plerixafor to chemotherapy to see whether it is better than chemotherapy at getting stem cells to move into the bloodstream so that they can be collected.

Timing of transplant

We know from research that people who have a very good response to their initial chemotherapy can stay free of myeloma (be in remission) for a long time, whether or not they have a stem cell transplant. So for these people, it may be better to wait until myeloma comes back before having a transplant. The PADIMAC trial is a phase 2 trial looking at giving a biological therapy, bortezomib (Velcade), a chemotherapy drug called adriamycin and a steroid called dexamethasone to people whose myeloma has come back. This combination of drugs is called PAD. The researchers want to know if people who have a good response to PAD can safely wait to have a stem cell transplant.

There is information about stem cell and bone marrow transplants for myeloma in this section.

People with myeloma are prone to kidney problems because of the high levels of protein (immunoglobulin) in their blood. A small number of people have kidney failure when they are diagnosed. At the moment these patients often need dialysis for life. Doctors think that plasma exchange may help damaged kidneys recover. Plasma exchange is a way of removing some of the proteins from the blood using a machine. The MERIT trial is trying to find out if plasma exchange, together with steroids and chemotherapy, will help damaged kidneys recover in people newly diagnosed with myeloma.

The EuLITE study is a European trial for people with multiple myeloma and severe renal failure. Some people have a type of myeloma with light chain proteins in their blood. Light chains are parts of the myeloma protein (immunoglobulin). The protein can be removed by a machine (dialysis) if it is damaging the kidneys. The EuLITE study wants to find out if people do better if they have dialysis for a longer time than usual (extended dialysis). You can read about the EuLITE study on the Myeloma UK website.

Radiotherapy has been used to kill myeloma cells for some time. But one problem has been that the high doses of radiotherapy needed to kill myeloma cells affect the rest of the body too. And this causes unwanted side effects. Targeted radiotherapy means that a radioactive molecule is attached to an antibody that looks specifically for myeloma cells. The antibody carries the radiation directly to the cancer cells. So the myeloma cells have a high radiation dose and are killed, but there are fewer side effects for the rest of the body.

There is a trial looking at using targeted radiotherapy before a stem cell transplant. The researchers want to find out if this is helpful for people with myeloma and to learn more about the side effects of this treatment.

A study is looking at the quality of life of people with myeloma. We know from research that having treatment and living with cancer can affect people's quality of life. But only a small amount of this research has been with people with myeloma. The researchers want to develop a questionnaire to assess and measure the quality of life of people at different stages of myeloma.

There is another study looking at how people cope with the symptoms of advanced myeloma and the side effects of treatment, to see if there is more that could be done to help them.