Non Hodgkin lymphoma research
This part of the non Hodgkin lymphoma (NHL) section is about research into the causes and treatments of NHL. You can find the following information
- A quick guide to what's on this page
- Why we need research?
- The research process
- Causes of lymphoma
- Scans to predict which treatment will work
- Finding out about lymphomas
Non Hodgkin lymphoma research
All treatments must be fully researched before they can be adopted as standard treatment for everyone. This is so that we can be sure they work better than the treatments we already use. And so we know that they are safe.
First of all, treatments are developed and tested in laboratories. Only after we know that they are likely to be safe to test are they tested in people, in clinical trials. Cancer Research UK supports a lot of UK laboratory research into cancer and also supports many UK and international clinical trials.
Researchers are looking into
- The causes of lymphoma
- Radiotherapy doses
- Biological therapies
- Stem cell transplants
- Retinoids (substances that are related to vitamin A)
You can view and print the quick guides for all the pages in the Treating NHL section.
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. Cancer Research UK supports a lot of UK laboratory research into cancer.
Tests in patients are called clinical trials. Cancer Research UK supports many UK and international clinical trials.
Our trials and research section has information about what trials are including information about the 4 phases of trials. If you are interested in taking part in a clinical trial for non Hodgkin lymphoma, 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 can refer you to the research team. The database also has information about closed trials and trial results.
All the new approaches covered here are the subject of ongoing research. Until studies are completed and new effective treatments are found, these treatments cannot be used as standard therapy for non Hodgkin lymphoma.
One study is finding out more about the causes of some types of lymphoma and chronic leukaemia. The researchers are looking at blood, bone marrow and tissue samples from people with white blood cell disorders, to discover more about the causes and possible future treatments.
Scans to predict which treatment will work
A study is looking at a new type of scan called magnetic resonance spectroscopy (MRS) to see if it can help to predict which type of treatment will work best for individual patients. MRS gives information about the activity inside a cancer, by looking at chemical changes. Researchers want to collect information from the scans and create a database so that they can see how patients' individual biological differences affect how well particular treatments work for them. Doctors hope they will be able to use this information in the future to choose the most appropriate treatment for patients. This trial is no longer recruiting patients and we are waiting for the results.
The IELSG 26 study is looking at tissue samples and PET scans to try to find the best type of treatment for a type of non Hodgkin lymphoma called primary mediastinal diffuse large B cell lymphoma (PMBL). PMBL is a very rare type of lymphoma that starts in the glands (lymph nodes) in the centre of the chest (the mediastinum). The study is trying to find out whether PET scans can show how well treatment has worked.
The MaPLe study is collecting information about the genes in lymphoma cells (molecular profiling). Changes to genes in certain lymphomas may encourage lymphomas to grow. It is possible that new treatments will be able to target these gene changes and may work particularly well in people who have lymphoma with these changes. The researchers will look at gene changes in lymphoma to identify who may be suitable for new targeted treatments. They will collect the information about these changes, the treatment people have and how well they work. And they will see whether it is possible to carry out molecular profiling of lymphoma in the NHS.
A lot of research is looking at new chemotherapy combinations for some types of NHL. Other trials are looking at new ways of giving standard chemotherapy drugs. Drugs and combinations being used include
CHOP chemotherapy has been the standard treatment for high grade NHL for many years now. A number of clinical trials are looking at using different combinations of chemotherapy drugs. One trial is comparing CHOP with GEM-P chemotherapy for people with T cell lymophoma. Other trials combine CHOP with biological therapies such as rituximab or Zevalin.
R-CHOP, which is CHOP chemotherapy together with rituximab, is now standard treatment for some types of NHL. Trials are taking place to find out how effective this combination is in treating different types and stages of non Hodgkin lymphoma. So far many of these trials show promising results.
Doctors often treat diffuse large B cell lymphoma (DLBCL) with R-CHOP. But one of the drugs can cause damage to the heart. If people already have heart problems or are very unfit, they can't have this treatment. Researchers for a phase 2 trial found that using gemcitabine chemotherapy could help people with newly diagnosed DLBCL who couldn't have R-CHOP. The 62 people who took part in the trial had a combination of rituximab, gemcitabine, cyclophosphamide, vincristine and prednisolone. This is called R-GCVP. You can read more about the results of this R-GCVP trial on our clinical trials database.
A trial is looking at another chemotherapy combination for people with diffuse large B cell lymphoma or Burkitt's lymphoma, if their doctor thinks there is a moderate or high risk of it coming back after treatment. This combination is called R-CODOX-M/IVAC, and it is a combination of 2 chemotherapy combinations that you have alternately. R-CODOX-M is rituximab, cyclophosphamide, vincristine, doxorubicin, and methotrexate. R-IVAC is rituximab, etoposide, ifosfamide and cytarabine. People on this trial also have cytarabine injected into their spinal fluid (intrathecal injection), to try to stop the lymphoma spreading to the central nervous system. The researchers want to find out how well this chemotherapy combination works in stopping the lymphoma coming back. They also want to find out more about the side effects it may cause.
Doctors usually treat diffuse large B cell lymphoma (DLBCL) with a combination of drugs called R-CHOP - rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone. A small trial called R-CHOP-B is looking at adding a type of biological therapy called bevacizumab to R-CHOP to see how helpful it is for this group of patients.
A trial is comparing GEM-P chemotherapy to CHOP for people with T cell lymphoma that has not been treated before. GEM-P is a combination of gemcitabine and cisplatin chemotherapy and the steroid methylprednisolone.
Doctors are also testing chemotherapy for rarer types of lymphoma. The WM1 trial compared the chemotherapy drugs fludarabine and chlorambucil for people with Waldenstrom's macroglobulinaemia or lymphoma of the spleen, who had not had treatment before. Fludarabine and chlorambucil are both effective treatments, but the researchers wanted to find out if one was better than the other. Both drugs were taken as tablets. The researchers presented some results at a conference in 2011. They showed that fludarabine was better than chlorambucil. When looking at overall survival, the researchers found about 6 out of 10 people taking chlorambucil (60%) were alive at 5 years compared to 7 out of 10 people (70%) in the fludarabine group.
The EORTC 21012 trial is looking at how well liposomal doxorubicin works on its own for people with mycosis fungoides that has come back or has stopped responding after at least 2 courses of treatment. Mycosis fungoides is a type of cutaneous T cell lymphoma (CTCL), a rare group of non Hodgkin lymphomas that affect the skin.
There is more information about trials for lymphoma on our clinical trials database.
A new chemotherapy drug researchers have been looking into is bendamustine (Levact), which was licensed in the UK in September 2010. The National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium SMC have not recommended it as a treatment within the NHS because the company making it have not put forward evidence to support its use. They may decide to put forward evidence in the future. But you may have it if your doctor thinks it is suitable for you.
Researchers in America and Canada gave bendamustine to people with B cell lymphoma, who have had other treatments that were no longer working including rituximab. They found that it worked in over 6 out of 10 people (60%) who had already had chemotherapy. And on average it carried on working for at least 9 months. The side effects were similar to other chemotherapy drugs and included feeling sick, low blood counts, tiredness, diarrhoea and constipation. We need more research to confirm these results and trials are continuing.
A phase 3 trial has looked into a chemotherapy drug called pixantrone (Pixuvri). The people taking part had aggressive (or high grade) NHL that had come back after having at least 2 courses of chemotherapy. In total, 140 people took part in the trial. Half the people had pixantrone and the other half had a standard chemotherapy drug. The researchers found that 14 out of the 70 people who had pixantrone (20%) showed no signs of lymphoma after treatment (complete response), compared to 4 out of 70 people (about 6%) who had standard chemotherapy. The results were similar after 18 months of follow up. Some of the more common side effects of pixantrone included low blood cell counts, a cough, feeling sick, abdominal pain, general weakness and feeling tired.
In 2014, NICE approved the use of pixantrone within the NHS for some people with B cell NHL. It is for people who have aggressive NHL that has continued to grow during treatment (refractory) or has come back after treatment (relapsed). You may have pixantrone if you have already had
- Treatment with rituximab
- 2 or 3 different courses of treatment
The PIX-R trial is looking at pixantrone for diffuse large B cell lymphoma or follicular lymphoma that has come back. The researchers are comparing the combination of pixantrone and rituximab with gemcitabine and rituximab in people who are not able to have a stem cell transplant.
NHL is often treated with radiotherapy. But doctors are aware that radiotherapy does have side effects that can be troublesome for people with NHL. A study comparing lower doses of radiotherapy with standard doses for NHL has recently published results. The researchers found that a lower dose of radiotherapy was as good as standard dose radiotherapy. Side effects were similar between the 2 groups, but reddening and darkening of the skin was less for people who had lower dose radiotherapy.
Doctors usually treat a rare type of NHL in the chest called primary mediastinal large B cell lymphoma (PMBCL) with chemotherapy and rituximab. After this, you may also have radiotherapy to your chest to reduce the risk of the lymphoma coming back. But radiotherapy can increase the risk of heart problems and of getting another cancer in the future. Some doctors think that leaving the radiotherapy out of treatment doesn't make it more likely that your lymphoma will come back. So the IELSG 37 trial is looking to see if it is safe to leave radiotherapy out of the treatment plan for some people with PMBCL.
Biological therapies are treatments that act on processes in cancer cells. They can work in different ways such as changing the way cells signal to each other or by stimulating the body to attack or control the growth of cancer cells. To look for biological therapy trials in NHL, go to our clinical trials database. Biological therapies being used and studied in NHL include
- Ibritumomab tiuxetan (Zevalin)
- Iodine-131 tositumomab (Bexxar)
- Epratuzumab (Lymphocide)
- Alemtuzumab (Campath)
- Inotuzumab ozogamicin
- Drugs to reduce tumour blood supply
- Bortezomib (Velcade)
- Gene therapy
A Cancer Research UK funded phase 3 trial reported in 2011 that adding rituximab to chemotherapy increased survival time for newly diagnosed patients with mantle cell lymphoma (MCL). The Mantle Cell P3 trial compared rituximab and chemotherapy to the standard treatment of chemotherapy alone. It found that adding rituximab to fludarabine and cyclophosphamide chemotherapy increased survival by about 8 months.
The rituximab versus watch and wait trial looked into whether giving rituximab to people with newly diagnosed follicular lymphoma can delay the time when they need to have chemotherapy and found that it did.
An international trial called PRIMA found that continuing with rituximab after finishing chemotherapy reduced the risk of follicular lymphoma coming back. 8 out of 10 people (80%) who had 2 monthly rituximab were still in remission after 2 years compared to just over 6 out of 10 (60%) who didn't have any treatment after their chemotherapy. People with follicular lymphoma now have maintenance treatment with rituximab for up to 2 years.
Trials of rituximab are continuing to find the best ways to use it. The PACIFICO trial is looking at different combinations of chemotherapy and rituximab. The researchers want to find out which combination of rituximab and chemotherapy is best for follicular lymphoma in patients 60 years of age and older. It is comparing rituximab, cyclophosphamide, vincristine, and prednisolone (a steroid) with rituximab, fludarabine, and cyclophosphamide.
Researchers for the NHL Ritux 2010 trial want to find out if adding rituximab to standard chemotherapy will improve treatment for children and young adults with B cell lymphoma or a type of leukaemia called Burkitt type acute lymphoblastic leukaemia.
The SABRINA trial is comparing different ways of having rituximab alongside CHOP or CVP chemotherapy for follicular lymphoma. You usually have rituximab through a drip into a vein, over a number of hours. In this trial, researchers are looking at giving rituximab as an injection just under the skin (subcutaneous injection), which only takes a few minutes. Researchers hope that giving the drug this way may reduce side effects and be more convenient. So far, the researchers have found that there is as much rituximab available in the bloodstream when you have it as an injection under the skin as when you have it as a drip into a vein. The researchers are now looking to see if subcutaneous rituximab works as well as rituximab through a drip, and what the side effects are.
The MABEASE trial is also looking at giving rituximab as an injection under the skin, alongside CHOP chemotherapy for diffuse large B cell lymphoma. This trial has closed and we are waiting for the results.
GP2013 is a new drug that is similar to rituximab. A trial is looking at GP2013 with chemotherapy for follicular lymphoma. The researchers want to find out if GP2013 and CVP chemotherapy works as well as rituximab and CVP chemotherapy. This trial has now closed and we are waiting for the results.
Zevalin is a monoclonal antibody attached to a molecule of radioactive yttrium (pronounced it-ree-um) and often written as Y-90. Zevalin is licensed for use in the UK in people with CD20 positive follicular B cell NHL. The Scottish Medicines Consortium (SMC) have not approved this treatment on the NHS in Scotland. And the National Institute for Health and Clinical Excellence (NICE) have not assessed it yet. So this treatment is not widely available.
The ZEST study is looking at Zevalin for people over 60 with diffuse large B cell lymphoma. The people taking part have had treatment such as R-CHOP and their lymphoma has completely disappeared (a complete response). Normally, your doctor would keep a close eye on you after treatment for signs of lymphoma coming back. In this trial the researchers want to see if Zevalin is better than observation after treatment for diffuse large B cell lymphoma, and to learn more about the side effects. This study has now closed and we are waiting for the results.
Bexxar is a monoclonal antibody, attached to a molecule of radioactive iodine. The antibody finds the lymphoma cells and the attached radioactive molecule kills them. It has mostly been tried for low grade NHL that has come back or is proving difficult to treat. So far it seems to help get more people into remission, and may mean you are in remission longer. Bexxar is also being looked at in diffuse large B cell lymphoma, the most common type of high grade lymphoma.
Epratuzumab (Lymphocide) is another type of monoclonal antibody that targets the CD22 protein found on B cells. It has been tested in people with high and low grade NHL that has come back or is proving difficult to treat. It has been tested on its own and in combination with rituximab.
Alemtuzumab (Campath) has been used in trials as a treatment for cutaneous T cell lymphoma. Now it is being tested in the CHOP-CAMPATH trial to see if giving it along with CHOP chemotherapy can help people with peripheral T cell lymphoma. This is a rare type of NHL where cancerous T cells circulate in the blood.
Nivolumab is another type of monoclonal antibody. There is a phase 2 trial looking at nivolumab for people with diffuse large B cell lymphoma (DLBCL) that has come back or is no longer responding to treatment.
Another trial is looking at nivolumab for follicular lymphoma. The researchers want to find out how helpful this drug is for people whose lymphoma has come back or is no longer responding to treatment.
Ofatumumab is another monoclonal antibody targeting the CD20 protein. The ORCHARRD study is comparing ofatumumab to rituximab for people who have DLBCL or follicular lymphoma that has come back. They want to see if ofatumumab works better than rituximab for people having treatment for the second time. In this study doctors are comparing DHAP chemotherapy and rituximab treatment with DHAP chemotherapy and ofatumumab, followed by a stem cell transplant.
The COMPLEMENT A + B trial is looking to see if a combination of ofatumumab and bendamustine works better than bendamustine alone for people with low grade lymphoma that hasn't responded to rituximab or has come back shortly after treatment.
CHT25 is a monoclonal antibody that targets the CD20, or IL-2, receptor found on some lymphoma cells. I stands for Iodine-131. So I-CHT25 is the CHT25 antibody attached to a radioactive iodine molecule. Doctors hope that the CHT25 will bind to the IL-2 receptors on the lymphoma cells, and the radioactivity will kill the cells. An early phase 1 trial found a safe dose of I-CHT25 that didn’t cause serious side effects. They also found that the drug helped about two thirds of the people in the trial. The researchers are now planning a phase 2 trial.
Mogamulizumab (KW-0761) is another type of monoclonal antibody. There is a trial looking at mogamulizumab for peripheral T cell lymphoma (PTCL) that has got worse or come back after treatment. PTCL is a type of NHL where the blood cells called T cells become cancerous.
Inotuzumab ozogamicin is another monoclonal antibody. Researchers think it may be helpful to add it to R-CVP chemotherapy for people with diffuse large B cell lymphoma who are unable to have standard R-CHOP chemotherapy. The INCA trial is comparing inotuzumab ozogamicin and R-CVP with gemcitabine chemotherapy and R-CVP.
Bevacizumab (Avastin) is also a type of monoclonal antibody. It targets a protein made by cells called vascular endothelial growth factor (VEGF). This stops the lymphoma from developing the blood vessels that it needs to grow. The R-CHOP-B trial is looking at giving R-CHOP chemotherapy with bevacizumab to treat people with diffuse large B cell lymphoma.
GA101 is a new monoclonal antibody that works in a similar way to rituximab. A trial is comparing GA101 with rituximab for low grade NHL. Researchers want to find out if GA101 is better at getting low grade NHL into remission than rituximab and if so, whether the remission lasts longer.
The GOYA trial is looking at GA101 for diffuse large B cell lymphoma. The researchers want to compare CHOP chemotherapy and GA101 (G-CHOP) with CHOP and rituximab (R-CHOP). They want to find out if diffuse large B cell lymphoma is more likely to go into remission with GA101 than rituximab and if the remission lasts longer, as well as what the side effects are like. This trial has now closed and we are waiting for the results.
Doctors call this type of treatment anti angiogenic treatment. Angiogenesis means growth of new blood vessels. Cancers need to grow their own blood vessels as they get bigger. Without its own blood supply, a cancer cannot continue to grow.
Thalidomide has been shown to slow the growth of cancer cells in some cancers, such as myeloma. Studies are now in progress looking into using thalidomide and other anti angiogenesis drugs for lymphoma. These types of treatments may eventually be useful to treat some types of NHL. But some researchers believe that they will only be useful in combination with other treatments already available, such as chemotherapy, radiotherapy and biological therapy.
A trial is looking at whether thalidomide can help to control angioimmunoblastic lymphoma after chemotherapy. Angioimmunoblastic lymphoma is a rare type of NHL. It is a high grade (aggressive) lymphoma that affects blood cells called T cells. The researchers want to find out if the chemo drugs fludarabine and cyclophosphamide help people with angioimmunoblastic lymphoma and to see if having thalidomide after chemo helps.
Another anti angiogenic drug is enzastaurin. The PRELUDE trial is looking to see if enzastaurin can help stop diffuse large B cell lymphoma coming back after chemotherapy, or keep it under control for longer.
Lenalidomide is another type of biological therapy. It works mainly by helping the body’s immune system target cancer cells. The EMERGE trial is looking at lenalidomide for people who have mantle cell non Hodgkin lymphoma. It is for people who have been treated with bortezomib (Velcade). Doctors often treat mantle cell lymphoma with chemotherapy. If mantle cell lymphoma comes back, doctors are not sure what to treat it with and have few treatments to choose from. The aim of this trial is to find out if lenalidomide can help people with mantle cell lymphoma after having bortezomib.
The SPRINT trial is also looking at lenalidomide for mantle cell lymphoma that is not responding to treatment or has come back after treatment. The researchers are comparing lenalidomide with the cancer drugs already used to treat mantle cell lymphoma, and to see how lenalidomide affects quality of life.
A trial is looking at lenalidomide for diffuse large B cell lymphoma (DLBCL) that has continued to grow during treatment, or has come back after treatment. This trial has closed and we are waiting for the results. Researchers for the LEGEND trial are looking at adding lenalidomide to the drugs gemcitabine, methylprednisolone and rituximab for DLBCL that has continued to grow during treatment or has come back.
Bortezomib is a proteasome inhibitor, a type of cancer growth blocker. It interferes with the chemicals inside cells, making proteins build up and kill the cells. Cancer cells are more sensitive to proteasome inhibitors than normal cells. A trial is looking at giving bortezomib with CHOP chemotherapy for mantle cell lymphoma. Researchers want to find out if this works better than just the chemotherapy on its own. Another small trial is looking at giving bortezomib in combination with other treatments.
The REMoDL-B trial is trying to find out if bortezomib can help to stop diffuse large B cell lymphoma (DLBCL) coming back after treatment. The standard treatment for DLBCL is R-CHOP, a combination of chemotherapy and a monoclonal antibody called rituximab. For many people, R-CHOP gets rid of the lymphoma cells (gets it into remission). But sometimes DLBCL does not go away, or comes back. This trial wants to see if adding bortezomib to R-CHOP will make it work better. This trial has now closed and we are waiting for the results.
There is information about these trials on our clinical trials database.
You may have bortezomib if you have mantle cell lymphoma and you have not had any other treatment and you cannot have a stem cell transplant. You have bortezomib in combination with rituximab, cyclophosphamide, doxorubicin and prednisolone.
Fostamatinib is a type of cancer growth blocker. It is a new drug that may work by blocking one of the signals that lymphoma cells need to grow and divide. One trial is looking at fostamatinib for diffuse large B cell lymphoma that has continued to grow during treatment (refractory) or has come back after treatment (relapsed).
Ibrutinib is another cancer growth blocker. The international SHINE trial is looking at ibrutinib capsules with bendamustine chemotherapy and rituximab for mantle cell lymphoma. The people taking part are over 65 years of age and have recently been diagnosed. This trial has now closed and we are waiting for the results.
Another trial looking at mantle cell lymphoma is the ENRICH trial. This is comparing ibrutinib and rituximab with ibrutinib and chemotherapy for people aged 60 or older.
The PHOENIX trial is looking at ibrutinib for people who have just been diagnosed with a particular type of diffuse large B cell lymphoma. Half the people taking part will have ibrutinib alongside the usual combination of treatment called R-CHOP. The other half will have R-CHOP and a dummy drug (placebo). This trial has now closed and we are waiting for the results.
The SELENE trial is looking at ibrutinib alongside chemotherapy and rituximab for low grade (indolent) lymphoma that has got worse or has come back after treatment. This trial has now closed and we are waiting for the results.
Idelalisib (Zydelig) blocks a protein called PI3K and helps stop cancer cell growth. It is a PI3K inhibitor. A phase 2 study looked at idelalisib in 125 people with indolent (low grade) NHL that had not responded to treatment or had come back within 6 months. More than half had follicular lymphoma. The average age was 64 years and most had stage 3 or 4 disease.
The trial team found that the cancer shrunk (responded) in nearly 6 out of 10 patients (60%). The average length of time before the cancer started to grow again (progression free survival) was 11 months. The most common side effects included an increase in the risk of infection from a drop in white blood cells, diarrhoea, a rise in the level of liver enzymes, and pneumonia. Researchers hope to study this drug further in larger trials, and in combination with other drugs.
The Scottish Medicines Consortium (SMC) have approved the use of idelalisib for people with follicular lymphoma in Scotland. They recommend it for adults who have had 2 previous treatments which have stopped working.
AZD1152 is a new drug that blocks enzymes. Cells need these enzymes to grow and divide. So blocking them may stop lymphoma from growing. Researchers are looking at AZD1152 for people with diffuse large B cell lymphoma which has continued to grow or has come back after chemotherapy and rituximab.
Alisertib is a new drug that blocks a particular enzyme, which may slow down cancer growth by killing the cancer cells. The LUMIERE study is comparing alisertib with the chemotherapy drugs pralatrexate or gemcitabine in people with peripheral T cell lymphoma. This study has now closed and we are waiting for the results.
Romidepsin (also called depsipeptide or FK228) is a new type of drug called a histone deacetylase inhibitor. It is made from a type of bacteria and works by stopping cells from dividing and growing. It has been looked at in trials for cutaneous T cell lymphoma (CTCL). This is a rare type of non Hodgkin lymphoma that affects the skin.
In America, two clinical trials found that romidepsin controlled CTCL for between 1 and 20 months in about a third of people who had the treatment. The Federal Drugs and Administration (FDA) have now approved it in America for people who have had other treatments which are no longer working. But before people can have it as a treatment in the UK it needs to be licensed and it may be a while before this happens. You can find out more about how drugs are licensed.
The RomiCar trial is looking at romidepsin and a cancer growth blocker called carfilzomib for peripheral T cell lymphoma that has come back, or treatment has stopped working. The researchers want to find the best dose for these 2 drugs, and see if the combination helps people with peripheral T cell lymphoma. They also want to learn more about the side effects of these drugs.
The PICLLE trial is an early trial looking at olaparib for mantle cell lymphoma and leukaemia that has stopped responding to treatment. Olaparib has already been looked at in clinical trials for solid tumours. The researchers want to find out the best dose of olaparib to give and how well it works for people with mantle cell lymphoma and some types of leukaemia.
Gene therapy aims to change the genes in cells in ways that will attack the cancer. This could be by
- Stopping genetic changes
- Replacing the altered genes of cancer cells
- Further changing the genes of the cancerous cells so that they are easier to destroy
- Changing the genetic make up of a virus so that it attacks cancer cells, but not normal cells
There is a small trial of gene therapy for B cell non Hodgkin lymphoma that has a protein called CD19 on the cell surface. Doctors want to take T cells from the blood of people with this type of NHL. Then they want to genetically alter the T cells. So when the T cells are put back into the body they will recognise the CD19 protein on the lymphoma cells and attack them. These altered T cells are called aCD19z cells. Patients on this trial will also have chemotherapy to kill off immune system cells that might attack the aCD19z cells. They will also have interleukin 2 (IL-2), which the researchers hope will make the genetically altered T cells live longer and work better. This trial is currently on hold.
Studies are looking at improving the way stem cell transplants are carried out for people with NHL.
It is possible to have treatment with your own stem cells. This is called an autologous transplant. But there is a risk that, after their treatment, the cells given back to you may still include some lymphoma cells. Scientists are trying to find new ways of getting rid of these from the stem cells. Research suggests that some of the new biological therapy drugs, such as rituximab, may help to remove these last remaining lymphoma cells. Doctors have been testing rituximab before and after autologous transplant for low grade lymphoma. They want to find out if this treatment will help keep the lymphoma in remission for longer.
The UK Haplo study is looking at using donor stem cells from a family member who is at least a 50% match with the person having the stem cell transplant. In most allogeneic transplants, the donor is someone who is a very close match to the person having the transplant. This is usually a brother or sister. It could also be from a donor who isn't a relative. But doctors can't find a match for about a third of those needing a transplant. An option for these people is a half matched transplant, where the donor is at least 50% match with the person having the transplant. In the past these transplants have been difficult to do. You can react to the donor cells, causing a severe immune response. But researchers think they have found a way to deal with this by using a drug called cyclophosphamide.
The aims of the UK Haplo study are to find out how well high dose cyclophosphamide works with a half matched stem cell transplant, how safe it is, and to learn more about the side effects and quality of life for people having this type of transplant.
The MAC UCBT trial is looking at using umbilical cord blood from unrelated donors after high dose chemotherapy. The aim of the trial is to find out if a transplant using cord blood from unrelated donors after intensive treatment is safe, and whether it helps people who need a stem cell transplant but don't have a stem cell donor. This trial has now closed and we are waiting for the results.
A procedure called a mini transplant has been investigated for people with NHL. In mini transplant, the chemotherapy doses are not high enough to destroy all your bone marrow cells. This can make it possible to treat some patients older than 50 because the side effects are less severe than those of a standard bone marrow transplant.
After the chemotherapy, you have bone marrow or stem cells from someone else (a donor) instead of your own marrow or stem cells. This is called an allogeneic transplant. The idea is that the donor marrow cells will replace your surviving bone marrow cells and make antibodies that will kill off the NHL cells. But the donor cells can also attack normal cells in the body. This is called graft versus host disease (GVHD).
Some people with NHL have a reduced intensity stem cell transplant or bone marrow transplant using cells taken from their brother or sister. This is called a sibling allogeneic transplant. After the transplant people need to take medicines to damp down the immune system (immunosuppressants). This helps to stop GVHD. But it also increases the risk of getting an infection.
The ProT4 trial is looking at giving extra T cells, a type of white blood cell after a mini transplant. Doctors hope that giving specific T cells called CD4 cells may help boost immunity and reduce the risk of infection. In this trial they are giving extra CD4 cells from the donor a few months after the transplant. This is called a donor lymphocyte infusion (DLI). The doctors also hope that the CD4 cells will recognise and kill any lymphoma cells left behind – something called the graft versus lymphoma (GvL) effect.
The MCL MiniAllo trial is looking at having a stem cell transplant using lower doses of chemotherapy, in combination with the biological therapy alemtuzumab (MabCampath) for mantle cell lymphoma. The aims of the trial are to see if a low intensity stem cell transplant is a safe treatment for people with mantle cell lymphoma. And to find out if it is better to have a transplant when people first go into remission, rather than wait until the lymphoma comes back.
The RIC UCBT trial is looking at using stem cells collected from the umbilical cords of newborn babies. The cells are given to people after a mini transplant. These cord blood transplants are for people who don't have a relative who can be their stem cell donor. Doctors hope that the umbilical cord stem cells will cause fewer side effects than adult stem cells.
The EORTC 21011 trial looked to see whether a drug called bexarotene (also called Targretin) could be effective in treating people with early stages of mycosis fungoides (a form of cutaneous T cell lymphoma, a rare group of non Hodgkin lymphomas that affect the skin). Bexarotene is a new type of retinoid drug. Retinoids contain chemicals that are similar to vitamin A. A treatment called PUVA is commonly used to treat mycosis fungoides. Although this treatment works well at first, the cancer usually comes back (recurs) and then you need more treatments with PUVA. If you have repeated courses of PUVA, your risk of developing non melanoma skin cancer increases. Doctors would like to be able to reduce the dose of PUVA and so reduce this risk. So this trial compared giving PUVA alone with giving PUVA and bexarotene.
The trial team found that PUVA with bexarotene worked just as well as PUVA alone and the side effects were acceptable. The researchers noted a trend towards people needing fewer PUVA sessions. But they could not rule out this happening by chance because not enough people took part in the trial. So it was not statistically significant.
The GemBex trial is looking at how well bexarotene and the chemotherapy drug gemcitabine work for cutaneous T cell lymphoma (CTCL) that has got worse, despite having had treatment to the skin and systemic treatment like interferon or chemotherapy.
Often after treatment for lymphoma, the disease appears to have gone. No lymphoma cells can be seen in your blood and bone marrow samples and you are said to be in remission. But there are often lymphoma cells left behind. This is called minimal residual disease (MRD). Scientists are exploring new ways of finding out if there are lymphoma cells left behind after the disease appears to have clinically gone - in other words, is in remission. These tests can help your doctors to find out how effective your chemotherapy has been in killing off all of your lymphoma cells, and whether your lymphoma is likely to come back (relapse).
Many tests are used, including
- Flow cytometry (a specialised microscope to look for markers on cells in your blood and bone marrow)
- Immunohistochemistry testing (a test for staining cells to see what's in them)
- Polymerase chain reaction (PCR ̶̶ a way of making copies of DNA)
Another test is PET scanning or positron emission tomography. After radiotherapy or chemotherapy has shrunk a tumour, harmless fibrous tissue can be left behind. On a CT scan, it may not be possible to tell if this tissue is fibrous or if it contains active lymphoma cells. It seems, from some very small studies, that PET scanning is able to do this. If doctors could check this with a scan, they would be able to tell more easily who needed more treatment and who didn't.
Although PET scanning is fast becoming one of the most important techniques used in helping to diagnose and manage many types of cancers, more research is needed before we know how important it will be in monitoring the treatment of NHL. There are a limited number of PET scanners throughout the UK as they are relatively new and very expensive. But your doctor will refer you to have a PET scan at your nearest centre if you need to have one done.
If you are interested in taking part in a clinical trial, you need to ask your own specialist if you may be suitable for any studies. Lymphoma is a big area of cancer research and most major treatment centres are continually involved in clinical trials.
A study is looking at the quality of life of people with follicular lymphoma. 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 follicular lymphoma. The researchers want to measure the quality of life of people at different stages of follicular lymphoma.
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