Treatment of low-grade non-Hodgkin lymphoma www.lymphomas.org.uk

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www.lymphomas.org.uk
Produced 28.02.2011
Due for revision 28.02.2013
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:
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the planning of treatment
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the aims of treatment
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the treatment of early-stage low-grade non-Hodgkin lymphoma
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‘watch and wait’ management of advanced low-grade non-Hodgkin lymphoma
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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:
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what kind of lymphoma you have
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the stage of your disease
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the effect the disease is having on your overall health.
Other important factors include:
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your age
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your blood test results
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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.
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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:
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who are well
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who have no B symptoms
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who have small lymph nodes which are not getting bigger quickly
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Lymphoma Association, PO Box 386,
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●
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:
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your lymph nodes begin to enlarge
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you develop B symptoms or begin to feel more unwell
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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.
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Lymphoma Association, PO Box 386,
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Registered charity no 1068395
[email protected]
www.lymphomas.org.uk
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:
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you have advanced B-cell follicular lymphoma (the commonest type of low-grade
non-Hodgkin lymphoma)
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your lymphoma produces a protein called CD20
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you are fit enough to cope with the side effects of the combination chemotherapy.
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Lymphoma Association, PO Box 386,
Aylesbury, Bucks HP20 2GA
Registered charity no 1068395
[email protected]
www.lymphomas.org.uk
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.
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Lymphoma Association, PO Box 386,
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Registered charity no 1068395
[email protected]
www.lymphomas.org.uk
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:
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you have stage III or stage IV B-cell follicular lymphoma, and
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you have relapsed after an earlier course of treatment, and
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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.
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Lymphoma Association, PO Box 386,
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Registered charity no 1068395
[email protected]
www.lymphomas.org.uk
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’.
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Lymphoma Association, PO Box 386,
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Registered charity no 1068395
[email protected]
www.lymphomas.org.uk
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 www.lymphomas.org.uk or
telephone the Lymphoma Association’s freephone helpline on 0808 808 5555.
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
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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.
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The Lymphoma Association does not necessarily agree with or endorse the comments included here.
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Lymphoma Association, PO Box 386,
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