Treatment of low-grade non-hodgkin lymphoma

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1 Produced Due for revision Treatment of low-grade non-hodgkin lymphoma Lymphomas are described as low grade if the cells appear to be dividing slowly. There are several kinds of low-grade non-hodgkin lymphoma and they are treated in a number of different ways. They are usually treated with chemotherapy and sometimes with radiotherapy. Some people will have treatment with antibody therapy. This article is an introduction to the treatment of this kind of lymphoma. It will discuss: the planning of treatment the aims of treatment the treatment of early-stage low-grade non-hodgkin lymphoma watch and wait management of advanced low-grade non-hodgkin lymphoma the treatments available for advanced low-grade non-hodgkin lymphoma. Planning treatment The treatment for low-grade non-hodgkin lymphoma will be planned according to your individual situation. The most important factors in planning your treatment will be: what kind of lymphoma you have the stage of your disease the effect the disease is having on your overall health. Other important factors include: your age your blood test results whether you have had unexplained weight loss, fevers or night sweats these are known as B symptoms whether or not you have other medical conditions. 1

2 The aims of treatment The aim of treating low-grade non-hodgkin lymphoma is to achieve a good-quality, prolonged remission with good quality of life. Some people with stage I or stage II low-grade non-hodgkin lymphoma have a chance of going into a permanent complete remission. For these people, the aim of treating the lymphoma will be to cure it. Advanced low-grade non-hodgkin lymphoma has a higher tendency to come back (relapse) and is difficult to cure completely. For most people with stage III or stage IV disease, therefore, the aim of treatment will be to control the lymphoma rather than cure it. This means that the doctors treat it like a chronic condition and you are likely to need treatment at regular intervals. However, there is reason to expect that this situation is changing. Recent important developments in treatment mean that people have better quality remissions of longer duration. It might not be too far in the future before advanced low-grade lymphoma is regarded as a potentially curable cancer. The treatment of early-stage disease Between 15% and 20% of people with low-grade lymphoma have disease at stage I or stage II at the time they first see their doctor. This means that, after completing all of the normal tests, the disease can only be found in one or two groups of lymph nodes. The standard treatment for people who have early-stage disease is radiotherapy to the affected lymph nodes and to the surrounding groups of nodes. Surgery to remove all the lymph nodes in the area is not the best treatment some lymphoma cells would be left behind after surgery and this means the lymphoma would be likely to come back. Some doctors suggest that people with early-stage disease might benefit from adding a short course of chemotherapy or antibody therapy to radiotherapy. Clinical trials will be needed to provide more information about this. Watch and wait for advanced-stage disease Many people who have stage III or stage IV low-grade non-hodgkin lymphoma do not require treatment straightaway. This means people: who are well who have no B symptoms who have small lymph nodes which are not getting bigger quickly 2

3 whose lymphoma is not threatening major organs, including the bone marrow. If this applies to you, your doctor might recommend watch and wait. You will have regular clinic appointments to check on your lymphoma and how you are feeling. You and your specialist will wait until your illness changes before considering treatment. For people who are suitable for this watch and wait approach the average time from diagnosis to starting treatment is about 18 months. Some people can go for many years without needing any treatment. It can be difficult to have a cancer that is not being treated. Many people find it hard to understand why no treatment is the best thing to do. It doesn t mean that you are too old, or that your disease is too advanced to treat. It means that it might be best to save yourself the side effects of treatment until your illness becomes worse. This advice might change in future years if clinical trials provide information that will change the treatment of people with no symptoms. On the basis of the experience doctors have had and the research done so far, however, this initial watch and wait approach is believed to be the best policy for this kind of lymphoma. Treatments for advanced-stage disease Your specialist will recommend starting treatment if: your lymph nodes begin to enlarge you develop B symptoms or begin to feel more unwell tests show that your major organs or bone marrow are affected. It is likely that you will need treatment more than once, and that you will experience different types of treatment over a period of time. The average time between treatments is 2 3 years. There are several treatments used for advanced low-grade lymphoma. There are a number of things that will be considered when deciding which of these treatments will be best for you: 1. What kind of lymphoma you have some lymphomas respond better to certain kinds of treatment than others and some treatments are not suitable for all lymphomas. 2. Whether you have been treated before certain treatments are recommended for people who are having treatment for the first time. Others are suitable for people who are having a second or third course of treatment. 3

4 3. Potential side effects especially for older people or other people who might have other health problems. Your specialists will need to be sure that you will be able to tolerate the side effects and that your treatment does not do more harm than good. 4. Previous treatment if you failed to respond to a treatment previously, or if it had only a very short-lived effect on your lymphoma, a different form of treatment is likely to be used next time. 5. Need for a rapid response if you have severe symptoms or are developing problems with a major organ, it is important to ensure that the lymphoma responds quickly to treatment. Some therapies produce a more rapid response than others. 6. Convenience the frequency of hospital visits, the need for admission as an inpatient and how long the treatment lasts altogether will be important factors when making a treatment choice. Taking all these things into account, your medical team will discuss with you what treatment options would be most suitable for you. In the following sections of the article we will briefly summarise the various treatment options that are currently available. Combination chemotherapy with rituximab Combination chemotherapy and rituximab is recommended as the standard first treatment for people with advanced B-cell low-grade non-hodgkin lymphoma who have not been treated before. Combination chemotherapy means giving several drugs together that act against the lymphoma cells in different ways. Some of the drugs are given as tablets and some are given through a drip or as an injection into your vein. Combination chemotherapy does not usually involve staying in hospital. You usually visit the hospital for a few hours on each day of the treatment. You will be given your drugs over a few days, followed by rest periods of 2 3 weeks between treatments, and the whole course takes about 6 8 months. This might be recommended for you if you are eligible. Being eligible means that: you have advanced B-cell follicular lymphoma (the commonest type of low-grade non-hodgkin lymphoma) your lymphoma produces a protein called CD20 you are fit enough to cope with the side effects of the combination chemotherapy. 4

5 Rituximab (MabThera ) is a monoclonal antibody therapy. Rituximab targets a protein called CD20 that is found on the surface of B cells, which are the cells that make up B-cell lymphoma when their growth is out of control. This results in the death of these B cells. Because rituximab is attracted only to B cells it does not damage other cells, so it does not have the same side effects as chemotherapy. Research has shown that combination chemotherapy together with rituximab is more effective than treatment with chemotherapy alone. Rituximab is most often given with a combination of drugs called CVP. This is abbreviated to R-CVP. CVP is short for cyclophosphamide, vincristine and prednisolone. Doctors also use rituximab in combination with CHOP chemotherapy. This is abbreviated to R-CHOP. CHOP is short for cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine) and prednisolone. Hydroxydaunorubicin can be damaging to the heart so CHOP is not suitable for anyone who already has heart disease. Rituximab can also be added to other combinations of chemotherapy but R-CVP and R-CHOP are the treatment regimens that are most commonly used as a first treatment. They can also be used as second or subsequent treatments, depending on how you responded to your treatments before. Combination chemotherapy on its own Sometimes combination chemotherapy is used on its own. CHOP and CVP are both used to treat advanced low-grade lymphoma and there are a number of other combinations that are in regular use or being developed. The chemotherapy combination you have will depend on the kind of lymphoma you have and on how you have responded to previous treatments. Fludarabine Some intravenous chemotherapy combinations are based on particular types of drugs called purine analogues. This group of chemotherapy drugs includes fludarabine and cladribine. Most experience in treating low-grade lymphoma has been with fludarabine. This drug is commonly used in the treatment of chronic lymphocytic leukaemia. Fludarabine can be given as an intravenous injection or in tablet form and a course of treatment usually lasts for 5 8 months. Fludarabine is often used in combination with other drugs, for example in FMD chemotherapy (fludarabine, mitoxantrone and dexamethasone) or in FCM (fludarabine, cyclophosphamide and mitoxantrone). Doctors are investigating the use of fludarabine and its combinations with rituximab. 5

6 Tablet chemotherapy Tablet chemotherapy has always been a common treatment for low-grade lymphoma. The side effects of tablet chemotherapy are often easier to tolerate than the side effects of intravenous therapy. This makes tablet chemotherapy a good option for anyone who is not fit enough to cope with intravenous combination chemotherapy. The most frequently used tablet is a drug called chlorambucil. A full course of treatment usually lasts about 6 months. Rituximab on its own Rituximab can be used on its own for people who have relapsed more than once after having chemotherapy or for people whose lymphoma does not respond to chemotherapy. It can also be used for people who are unable to cope with the toxic side effects of chemotherapy because of other health problems. Rituximab maintenance therapy Rituximab is given to some people as a maintenance treatment after they have gone into remission following chemotherapy. Research confirms that using rituximab in this way helps to prolong remission for significant periods. Rituximab maintenance might be suitable for you if: you have stage III or stage IV B-cell follicular lymphoma, and you have relapsed after an earlier course of treatment, and you go into remission after having a further course of chemotherapy or chemotherapy-rituximab treatment. Maintenance rituximab is given once every 2 3 months. At the moment it is given for a maximum period of 2 years. It is hoped that NHS guidance will be changing soon to allow rituximab to be offered as a maintenance therapy for people who have gone into remission after their first course of treatment. Radioimmunotherapy Radioimmunotherapy is a combination of antibody therapy and radiotherapy. A tiny radioactive particle is attached to an antibody that targets the CD20 molecule on the B cell. The action of the antibody is combined with the delivery of a dose of radiation direct to the lymphoma cell. Because radioimmunotherapy targets the B cell in particular it avoids damage to healthy cells. Zevalin and Bexxar are radioactive antibodies you might hear of. 6

7 Radioimmunotherapy can be given after chemotherapy to make remission last longer. Radioimmunotherapy can also be used for people who have relapsed following earlier treatments with chemotherapy and rituximab or for people whose lymphoma does not respond to other treatments. Radioimmunotherapy is not widely used in NHS hospitals yet but it is hoped that results of research will change this situation in the near future. Steroids The word steroid refers to a large family of similar drugs. They are all drugs that imitate hormones produced naturally by the body. They can help kill cancer cells and reduce inflammation. Steroids can be given with chemotherapy or on their own. The most commonly used steroid is called prednisolone and this is the P in CHOP combination chemotherapy. Steroids are given as tablets or sometimes intravenously. Steroids are not a long-term treatment for lymphoma, but they are very effective for controlling symptoms and for reducing the disease quickly. Steroids are particularly useful for people who are not well enough for chemotherapy or for people with severe symptoms of lymphoma. High-dose chemotherapy and stem cell transplantation Specialists sometimes recommend treatment with high doses of chemotherapy for advanced low-grade non-hodgkin lymphoma as a first treatment or as a treatment to follow standard chemotherapy. This is because they believe that this can produce a good-quality, prolonged remission. A stem cell transplant involves a stay in hospital of 2 4 weeks. These high doses of chemotherapy drugs cause permanent damage to your bone marrow and you need a transfusion (or transplant) of stem cells to allow your marrow to recover. Stem cells are immature cells that grow into new blood cells. Following the transplant, they find their way back to your bone marrow and replace the damaged cells so that you can begin to produce vital blood cells again. Stem cell transplants for lymphoma usually involve using your own stem cells, which are collected before you have the high-dose chemotherapy (an autologous transplant). Less commonly, stem cells from a donor are used (an allogeneic transplant). The cells from the donor are like giving you a transplant of a new immune system. These new immune cells will mount an attack against your lymphoma cells. This is known as the graft versus lymphoma effect. 7

8 A donor transplant is a more complex and risky procedure and it is only used for people who have relapsed following other treatments. Some donor transplants use reduced-intensity conditioning, which means giving lower doses of chemotherapy and radiotherapy before the stem cell transplant. This is done to make them safer for older people who might not tolerate high-dose chemotherapy. More information This article is an edited extract from our booklet, Low-grade non-hodgkin lymphoma. For a copy or for more information, visit our website at or telephone the Lymphoma Association s freephone helpline on Talk to your key worker if you have any concerns about your health or treatment. The Lymphoma Association cannot provide information about individual diagnosis or treatment. The information provided by the Lymphoma Association is not a substitute for advice from your health professionals. About our publications: The Lymphoma Association is committed to the provision of high quality information for people with lymphoma, their families and friends. We produce our information in accordance with nationally recognised guidelines. These include the DISCERN tool for information about treatments, the NHS Toolkit for producing patient information, and the Campaign for Plain English guidelines. Our publications are written by experienced medical writers, in close collaboration with medical advisers with expertise in the appropriate field. Textbooks and professional journals are consulted to ensure that information is as up to date as possible. References are provided where they have been used. Some publications are written by professionals themselves, acting on guidance provided by the Lymphoma Association. Our publications are reviewed every two years and updated as necessary. Our publications are reviewed by a panel of volunteers with experience of lymphoma. Publications are also reviewed by members of the Lymphoma Association helpline team, who have many years collective experience of supporting those with lymphoma. In some instances, our publications are funded by educational grants from pharmaceutical companies. These sponsors do not have any involvement in the content of a publication. They are not invited to see the content and have no editorial input. Lymphoma Association Views expressed in this publication are those of the contributors. The Lymphoma Association does not necessarily agree with or endorse the comments included here. 8

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