TREATMENT

If you have been diagnosed with WM you might have no treatment at all for a while so called, Watch and Wait  or you might have one or more of the following treatments:

  • chemotherapy drugs
  • steroids
  • monoclonal antibodies
  • stem cell transplant
  • novel agents

You might also need other treatments if you have thickening of your blood, if your blood counts are low, or if you have side effects from the chemotherapy drugs. These additional treatments are called ‘supportive’ treatments.

The treatment you will be given will depend on your particular circumstances. It will depend on the results of all the tests, on your symptoms, your age and general health.

Watch and Wait?

The first response of most people diagnosed with cancer is to look for immediate treatment. This is not always needed as WM is usually slow moving and may take years to develop, or in some cases never develop. Most symptoms are not usually life threatening. Hence patients may be put on 'watch and wait'. This decision is determined by the relative progression of the disease and the severity of the patient’s symptoms. When a patient is first diagnosed it is important to begin recording blood test values and symptoms to establish a baseline. It's usual also to have an initial scan to see if other organs are involved.

As additional laboratory tests are performed and patient symptoms are monitored, a pattern will become evident which will indicate a rate of disease progression. In many WM cases, there will be very little change in status from visit to visit. For these patients a strategy of W&W may be an option. Many patients keep a record of their key tests and relate them to their general well being and symptoms.

W&W avoids the use of treatments, which could have side effects, until treatment is absolutely necessary. The question is: “By delaying treatment am I allowing WM to become more difficult to treat in the future or am I allowing symptoms to progress to the point that they cannot be easily managed?” This question can only be answered by you and your specialist after a review of your individual test results and symptoms.

Plasmapheresis

Not a treatment as such, but for patients diagnosed with high levels of IgM producing symptoms, plasmapheresis is a rapid way of reducing them. In some ways like kidney dialysis, the patient is connected by a line in each arm to an apheresis machine for 2-3 hours, the heavier IgM is centrifuged off and the blood returned. There are very few side effects. This gives immediate relief typically lasting for a month or two and a breathing space whilst doctor and patient negotiate the best treatment. The photos show a day patient at the National Blood Transfusion centre at Bristol. The nurse is programming the apheresis machine.


Plasmapheresis at the Bristol National Blood & Transplant Centre

Chemotherapy

Chemotherapy (treatment with anti-cancer drugs) can be given to destroy the abnormal B cells. Several chemotherapy drugs have been proved to be effective in WM, mostly originally developed for more common blood cancers (so called Orphan Drugs). Some of these drugs are given intravenously (into a vein through a plastic tube called a cannula), some are taken by mouth in tablet or liquid form and some are given subcutaneously (injected just under the skin).

When treating WM, two or more drugs with different actions may be used together. These drug combinations are more effective than single drugs in attacking the abnormal B cells. The drugs are given in cycles over a period of a few months, meaning that you will have treatment some weeks but not others. This allows healthy blood and bone marrow cells to recover between treatments.

There are a number of different combinations and doses of drugs used. Your treatment will be individually tailored by your medical team to ensure that you are having the best and most suitable course of treatment for you. The combination will depend on your age, what symptoms you have, how severe your symptoms are and your blood counts. It will also depend on what treatments you might possibly require in the future (certain drugs are best avoided  if you might need a stem cell transplant later on as they deplete stem cells).

Chemotherapy Drugs

Conventional chemotherapy treatments commonly used to treat WM generally have the effect of chemically disrupting DNA in rapidly dividing cancer cells.  They also affect other rapidly dividing cells, and thus may affect the stomach lining, causing nausea and hair loss.

Chlorambucil: Chlorambucil is a commonly used and long standing chemotherapy drug (a purine analoge) and is taken in tablet form. It is usually taken daily for a period of time specified by the doctor. Its side effects are normally mild.  Now usually given to older patients where more intensive chemotherapy might not be tolerated.  The main limiting factor for use may be a drop in white count- mainly Lymphocytes which can allow opportunistic infections.

Fludarabine: Fludarabine can be given as tablets or intravenously, usually every day for 5 days. Treatment is usually repeated every 3–4 weeks for 6–8 months. This chemotherapy produces a more rapid response than Chlorambucil, but its side effects can be more severe.

Cladribine (2CDa): is a similar type of drug to Fludarabine and has similar side effects, but it is given using a different schedule. It is can be given intravenously or subcutaneously every 6–8 weeks for two courses.


Chemotherapy bay at University College Hospital, London

Other chemotherapy drugs: Other types of traditional chemotherapy drugs such as Cyclophosphamide, Doxorubicin (H, Hydroxydaunorubicin)  and (O)Vincristine may be used improve effectiveness. These drugs are typically given in combinations known as ‘CHOP’ or ‘CVP’, in which the ‘P’ stands for Prednisolone, a type of steroid that is given at the same time as the chemotherapy drugs (see below). These combinations are usually given every 3 weeks for six cycles.   Combinations containing Vincristine may cause existing nerve damage caused by the WM to become more severe.   If you are suffering from any peripheral neuropathy (i.e. tingling in hands or feed for instance) at time of treatment you should make this clear to your doctor. 

Other combinations of chemotherapy drugs and other agents may also be used – your medical team will discuss these with you.  One standard is now R-CHOP - a mixture of the above with Rituximab® - see below.

To an extent there is a degree of 'postcode prescribing' in the NHS at present, particularly in the availability of Rituximab based chemotherapies- you are strongly advised to ask specifically what is available in your area, and compare with other patients on line.

Potential side effects of chemotherapy

All chemotherapy drugs have potential side effects. These vary from patient to patient and the different drugs used. It is important to remember that most side effects are manageable and will resolve once treatment is finished.

Common side effects of chemotherapy include nausea, loss of appetite, change in bowel habit, hair thinning or loss, and an increased tendency to develop infections, bruising and bleeding.    Anti-nausea drugs such as Domperidone or Ondansetron are usually given to reduce sickness. It’s always good to take them sooner than later as once sickness starts it’s difficult to stop.

Steroids are used to reduce inflammation in many medical conditions. In WM they also appear to help a process called ‘programmed cell death’. This means that steroids can trigger the destruction of the abnormal B cells. When used in combination with chemotherapy, steroids can make your lymphoma more responsive to the chemotherapy drugs and therefore make the treatment more effective. In the treatment of WM, steroids are usually given by mouth in tablet or liquid form, but they can also be given intravenously.

Potential side effects of steroids. Side effects of steroids do vary. It is important to remember that each person’s reaction to steroids can be different and that side effects, if any, are temporary and should resolve when the steroids are stopped. Common side effects of steroids include indigestion, increased blood sugar, increased blood pressure, increased risk of infection, increased appetite, mood changes and weakness due to muscle wasting.

If treatment results in very low white cell counts, patients may be given injections of Colony Stimulating Factor (GCSF) drugs which boost the production of  white cells.   In some cases these can be self administered at home between cycles of chemotherapy as the lowest counts (the nadir) occur several days after each chemotheraphy cycle. 

Monoclonal antibodies

Monoclonal antibodies are advanced drugs that recognise, target, and attach to certain proteins on the surface of some cancer cells. This marks out the cells for destruction by the body’s immune system. A monoclonal antibody called Rituximab is commonly used in the treatment of WM, alongside chemotherapy and/or steroid treatment. Such combinations are known by their initial letters eg R-CHOP.   Rituximab binds to a B cell protein called CD20.

Rituximab (Rituxin in the USA, Mabthera in EU) is given slowly into your vein the first time it is given (it may take up to 8 hours) and then it is given a more quickly on subsequent infusions if it is well tolerated.  Usually an antihistamine such as Piriton is given first to reduce any chance of infusion reactions, which usually take the form of flu-like symptoms.

Monoclonal antibodies themselves have few side effects, but in combinations such as R-CHOP the other components may do. You can experience flushes, sweats, a fast pulse rate and a decrease in blood pressure during the infusion of Rituximab, which is why the first infusion is given slowly. Most people tolerate this drug without problems, however.

Other Monoclonal Antibodies are being developed and gradually coming into use. Ofatumamab® has been used in WM but is not widely available in UK.  

Less commonly used drugs and new drugs

Other drugs that have been shown to be effective in clinical trials, either alone or combined with other drugs, include Bortezomib (Velcade®), Bendamustine®Thalidomide and Ofatumumab.  These drugs are still being tested in clinical trials and are not yet in general use. Permission to use these drugs usually needs to be specifically sought from the local regulatory bodies by the doctor before they can be used. New drugs are becoming available all the time and continue to be tested in clinical trials. If a local Clinical Commissioning Group refuses an expensive treatment at first, the Cancer Drugs Fund may be an alternative-particularly for Bendamustine - ask your specialist.

Novel Therapies

Over time treatment has moved from a scatter gun approach to targeted therapies affecting WM cells at the molecular level, without damaging the rest of the body.  The latest drugs emerging from the USA such as Ibrutinib (Imbruvica) and Idealisib® seem to have very significant effects over a range of B related cell malignancies such as WM, CLL, and Mantle Cell Lymphoma.   For instance Ibrutinib® is a BTK inhibitor (Bruton’s Tyrosine Kinase) which affects programmed cell death.  It has just been approved in the USA for use (but not yet specifically for WM).  Such developments, with very few side effects (Ibrutinib is taken orally), have the potential to change WM from an incurable but treatable disease to a chronic one with long term medication - similar in a way to diabetes and insulin.    The question of affordability of these novel agents in the NHS is at present unresolved!    We hope that UK trials for these novel agents will be forthcoming soon.

Stem cell transplantation

This is also known as 'peripheral blood stem cell transplantation'. This type of treatment is sometimes considered for younger (under 65 possibly), fitter, people with WM who are able to tolerate the intensity of the treatment and where previous treatment has failed or has led to relapse. Stem cells can be obtained either from your own blood or from a matched donor and they are infused (dripped slowly through a cannula into your vein) after you have had a course of high-dose chemotherapy to reduce the WM disease to a low level

Autologous stem cell transplant: When you act as your own donor, this is known as an ‘autologous’ transplant. In this form of transplant your own stem cells are collected. Having the cells collected is a bit like giving blood. These cells are stored frozen until after you have had your course of high-dose chemotherapy to kill any remaining WM cells. Your stem cells are then returned to you. They make their way to your bone marrow, where they form new blood cells (‘engraft’) to restore your bone marrow to normal function.


Collection of stem cells


Stem Cell Harvest
2 million stem cells!

This form of stem cell transplant is not usually a cure, but it can lead to you having a long-lasting remission, meaning that the disease can stay at a very low level for quite a long time before further treatment is needed.  Typically the whole process will last two weeks in hospital.
Allogeneic stem cell transplant: When the stem cells come from another person this is known as an ‘allogeneic’ transplant. The donor might be a brother or sister or someone not related to you but whose tissue type matches yours (form the Anthony Nolan Bone Marrow Register for instance). In this type of stem cell transplant, the donor’s stem cells produce donor blood cells in your bone marrow, and these cells can directly fight against any leftover lymphoma cells so that the disease is treated using the donor’s immune system as the weapon.

While this form of transplant can offer the possibility of cure for some people with WM, it is a more hazardous procedure than an autologous transplant and your general health has to be good before you would be considered for it. The failure rate is higher than autologous transplants and you would need to think about the risks and benefits very carefully before embarking on this treatment. Your medical team would discuss this option in detail with you if they felt you could benefit from it.

Where to be treated?

To some extent there is a postcode lottery in these difficult economic times between different hospitals, and you may find that new treatments available in the USA or EU are not available in the UK or one or more of its component countries. It's usual for teaching hospitals to have greater flexibility in offering the latest treatment, and they are more likely to run trials of new therapies. They will also have advanced MRI/CT scanners and availability of specialists to deal with side effects of WM such as Peripheral Neuropathy. Some very large centres have dedicated WM clinics.

WMUK works with other organisations to try to promote new treatments and drug trials in the UK.   The trials gateway for UK trials is at UK Trials Gateway   you can interrogate this by disease or by drug type.