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

First of all, 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 recruiting in the UK. 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.

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.

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

• Velcade (bortezomib)
• Thalidomide
• Lenalidomide (Revlimid)
• Pomalidomide
• Carfilzomib
• Vaccines
• Chemical growth factors (cytokines)
• CNTO 328
• Drugs that block cell growth

Velcade (bortezomib)

Doctors use velcade (bortezomib) for people with myeloma that has come back, or has continued to grow. Velcade is a type of biological therapy called a  proteasome inhibitor. This means it blocks normal cell processes that break down and recycle proteins inside cells. If this machinery is blocked, the cell dies. Velcade affects cancer cells, but normal cells do not seem so sensitive to it. 

An international study looked at whether you can have Velcade as an injection just under the skin (subcutaneous injection) rather than into a vein (intravenously). The trial team released their results at the American Society of Haematology meeting in December 2010. The trial recruited 222 people with myeloma. The researchers found that having Velcade as an injection under the skin had similar results to having it injected into a vein. And there were fewer reports of tingling and numbness in the fingers and toes (peripheral neuropathy) in people having it as an injection under the skin.

From research so far, we know that Velcade 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 Velcade alongside chemotherapy as the first treatment for myeloma can have a very good response. Myeloma disappears (complete remission) in more people who have Velcade with chemotherapy than in people who have chemotherapy alone.

The PADIMAC trial is looking at a combination of the drugs Velcade (bortezomib), 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.

Velcade in combination with doxorubicin chemotherapy and dexamethasone (PAD) is also being used for people who have had chemotherapy before, if their myeloma comes back or stops responding to treatment. The researchers want to find out ho well this treatment works for people who have already had treatment. 

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

The MYELOMA 11 trial is looking at combining Velcade with other biological therapy drugs such as lenalidomide and thalidomide, the chemotherapy drug cyclophosphamide, and the steroid, dexamethasone.

Thalidomide

Thalidomide is a drug that affects the chemicals cells use to signal to one another. Your specialist may say it is a cytokine modulator, which means the same thing. It can affect all sorts of cell processes, including the growth of cancer cells. Thalidomide is also known as an anti angiogenic drug. Angiogenesis means growth of new blood vessels. Tumours need to grow new blood vessels as they get bigger, so an anti angiogenic drug is one that helps to stop this. We already know that thalidomide can be very helpful for myeloma that has come back or stopped responding to other types of treatment.

A French trial for people aged 65 to 75, newly diagnosed with stage 2 or 3 myeloma, reported in October 2007. Survival rates were significantly better when thalidomide was added to the standard therapy of melphalan and prednisone. Adding the thalidomide did increase side effects, such as risk of infection, numbness and tingling in hands and feet, risk of blood clots and severe tiredness. Blood clots have been shown to affect up to 25 out of 100 people (25%) having this treatment. Doctors may try to prevent this happening by giving drugs that thin the blood to people thought to be at higher risk of clots.

Some specialists suggest thalidomide 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 a similar drug 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.

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.

Pomalidomide

Early trials have been looking at a new drug called pomalidomide. A phase 2 trial that was reported at the 2010 American Society of Haematology meeting looked at pomalidomide and dexamethasone in people with myeloma who had already been treated with Velcade and Revlimid. The results were promising but we need larger studies.

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 severe tingling and numbness in the fingers and toes (peripheral neuropathy), which can be a side effect of Velcade.

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 know if this treatment will work as yet.

Chemical growth factors (cytokines)

Cells produce a number of chemical 'growth factors'. Scientists call these chemicals cytokines (pronounced sy-toe-kines). Cells called stromal cells, found in the tissues that support the bone marrow, make a number of these growth factors, including 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, 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 underway to try and find ways to block these growth factors because that may help to stop the growth of myeloma cells.

CNTO 328

CNTO 328 is a type of monoclonal antibody (MAB). 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 a new biological therapy called CNTO 328 with bortezomib works better against myeloma than bortezomib on its own. The trial also aims to find out about the side effects of CNTO 328. This trial has closed and we are waiting for results.

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 aims of this trial are to see if adding panobinostat to bortezomib and dexamethasone helps this group of people. And to learn more about the side effects of this drug combination. 

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, if the patient has already had at least one treatment, and has had, or is not suitable for, a bone marrow or stem cell transplant. In October 2008, the SMC (Scottish Medicines Consortium) and in July 2009 the AWMSG (All Wales Medicines Strategy Group) decided that Caelyx should not be available on the NHS in Scotland and Wales for this type of treatment.

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 more 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 down the destruction of bone. They are mainly used to treat the bone thinning disease osteoporosis. But they have also been used to treat the symptoms of cancers affecting the bone including myeloma. In a phase 3 trial called Myeloma IX researchers compared two types of bisphosphonates, injections of zoledronic acid with clodronate tablets. Everyone in the trial had chemotherapy. They found that the 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 but it was still rare - 4 out of 100 people (4%) having zoledronic acid compared to less than 1 in 100 in those 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 are normally given 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 chemotherapy, followed by 'stem cell rescue' or 'bone marrow transplant', has been used to treat myeloma for some time. Doctors continue to work hard 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 much over 45. Now doctors are willing to use it for patients up to 70 provided they are fit enough to get through it. The doctors researching this treatment also want to improve the length of time that this type of treatment can keep myeloma in remission, with the hope of eventually being able to cure it. The latest developments are

• Double transplant
• Mini transplant
• Treatment for sore mouth

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 will increase the risks and side effects, so doctors are continuing to research this.

Researchers are also looking into giving a second transplant when myeloma relapses. 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 will first have treatment with bortezomib, doxorubicin and dexamethasone. This is called the PAD regime, and is being looked at on its own in another trial. You will have between 2 and 4 cycles of this treatment, depending on how well it works. Then one of two groups of patients will have a second transplant of their own stem cells. It is common for doctors to try to collect enough stem cells for 2 transplants, so you may not have to have more stem cells collected (or 'harvested'). The other group of patients will have 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. (This means 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 do have more risks and side effects than a transplant using your own cells. So they are not suitable for everyone.

At the moment they 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 the following approach: chemotherapy to get the myeloma under control, followed by intensive chemotherapy and 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 it works if it is only given before your transplant. They also want to find out if palifermin causes or worsens cataracts (clouding over of the lens in the eye). This trial has closed and we are waiting for the results.

There is more general information about stem cell and bone marrow transplants in the about cancer section of CancerHelp UK.

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. A trial called MERIT has been trying to find out if plasma exchange, together with steroids and chemotherapy, will help damaged kidneys recover in people newly diagnosed with myeloma. This trial is no longer recruiting patients and we are waiting for the results.

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 receive the highest radiation doses and are killed, but the rest of the body is not as affected.

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. 

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.

There is a 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. This trial has now closed and we are waiting for the results.