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CLL Treatment

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When the decision has been made that treatment is necessary, or when you are approaching treatment, it is valuable to learn as much about your CLL as possible. This will enable you to talk to your consultant about your options and this section will give you some important information to help you do that.

In the majority of cases, CLL is not yet curable, but it is very treatable, and it is usually possible to control the disease. You may well have a normal life span with a good quality of life after diagnosis.

The treatments available for CLL are improving and changing. They are determined by current NHS funding regulations, which might make you eligible or not eligible for different treatments. Whether you have had treatment before and how many lines of treatment will also be a consideration.

When to start treatment

Many people with CLL don’t need to begin treatment immediately after being diagnosed. If you do need to start treatment, your treatment options may depend on your general health, including any other health problems, and also your wishes.

You will need to have regular blood checks to see whether your disease is progressing. This is often called ‘watch and wait’. However, it may be more helpful to use the terms ‘medical monitoring’ or ‘active monitoring’. It is important that you attend these appointments so that your consultant can track your CLL, and so that your consultant can talk to you about how you are feeling.

The indications to start treatment may include:

NOTE: A rising lymphocyte (white blood cell) count alone is not usually an indication that treatment is necessary.

The aim of starting treatment is to improve symptoms, improve blood counts and prolong survival with as good a quality of life as possible. Your consultant will not recommend treatment until it becomes necessary. Current clinical thinking is not to start treatment immediately after diagnosis as there is no evidence that this improves the outcome.

Tests to help determine treatment options

The following tests may be carried out:

Bone Marrow aspiration and biopsy

This involves extracting a small amount of fluid from the marrow space and also a sample of the more solid part of the marrow for analysis in the laboratory. This is called a bone marrow biopsy or trephine biopsy.


Ultrasound and, more frequently, CT (Computed Tomography) scanning enables your consultant to more accurately assess enlarged lymph nodes and spleen.

FISH test, also known as Cytogenetic tests

FISH stands for Fluorescence In Situ Hybridisation. The test looks at the genetic make-up of your CLL cells, as this can influence your treatment options. If you have an abnormality of the chromosomes in your CLL cells, known as a 17p deletion, TP53 deletion or mutation, you are less likely to respond to chemotherapy, and alternative treatments will be considered. Note: FISH does not test TP53, and another test will be required for this.

More information on tests available is given in the section on prognostic factors.

What type of treatment will I have?

Treatments have improved enormously over the last twenty years, and even more in the last ten. It is now normal to use combinations of drugs, and these have been increasingly successful.

Any treatment will be tailored to your particular health profile and the risk profile of the CLL itself. Your consultant will advise you on the best available for you.

The standard, first-line treatment for most patients until recently, was chemo-immunotherapy. However, this is now rarely used, except in certain circumstances. If used at all, it is a combination known as FCR.


FCR stands for the three drugs Fludarabine, Cyclophosphamide and Rituximab. Rituximab is an example of a monoclonal antibody drug (immunotherapy). Fludarabine and Cyclophosphamide are examples of ant-cancer drugs. If you are less than 65 years of age, fit, and have no other medical problems, you may be treated with FCR. However, there is a general move towards the more targeted treatments.

FCR is usually given in ‘cycles’. Each cycle is 28 days long, and you’ll typically have treatment each day for five days, then have a break for 23 days without treatment. You may have up to six cycles.

Fludarabine and cyclophosphamide are tablets.

Rituximab is given as an infusion into a vein. Some terms you may hear for this are ‘drip’ and ‘intravenous’ or ‘IV’. Usually only the first day of each 28-day cycle requires you to attend hospital (for the Rituximab infusion) and the remaining four days you finish the chemotherapy in tablet form at home.

Some other treatments you may be offered are:


In some cases, you may be offered rituximab alongside other drugs. Rituximab is usually given as an infusion.


Ibrutinib is a targeted drug called a Bruton’s tyrosine kinase (BTK) inhibitor which works by blocking signals within cells that are important for their survival. This drug is particularly useful if you have certain genetic characteristics known as 17p deletion, 11q or TP3 mutation.

Ibrutinib may be used on its own, or in combination with other drugs, for example, Venetoclx. Ibrutinib is taken in capsule form, usually once a day.


Idelalisib blocks some of the proteins inside cancerous cells that encourage the cancer to grow. It may be used along with rituximab. It may be used to treat you if you have not responded to other treatments. It is taken in tablet form.


‘Venetoclax is a new treatment, known as a BCL2 inhibitor, which blocks the growth of CLL cells and promotes cell death. Currently, Venetoclax is used if a first treatment hasn’t worked as well as expected, or if CLL has returned after previous treatment. It is taken in capsule form once a day. Venetoclax may also be administered together with other drugs such as Ibrutinib, obinutuzumab or rituximab, in combination, to increase effectiveness.


Acalabrutinib is new treatment which acts in a way similar to ibrutinib, but which may have fewer side effects in some patients. Both these drugs are very similar and block the same pathway in the CLL cells’ metabolism.


This is also a new treatment which operates in a similar way to Ibrutinib and Acalabrutinib. It is only available for certain patients, and your consultant will advise if it is suitable for you.

A list of all current treatments available can be found here.

Chimeric Antigen Receptor T cells (CAR-T cells)

In CLL, the normal immune system has become very weak. In CAR-T cell therapy, a CLL patient’s T cells are removed, manipulated in a laboratory to make them better able to kill CLL cells. They are then returned to the patient. At present this is not available for CLL patients in the UK.

Clinical Trials

Your doctor may suggest that a clinical trial could be an option for you. Please see the separate section below on trials for more information.

Side effects from treatment

You may experience side effects from your treatment, although this varies greatly between patients, and depends on the type of treatment you receive. Chemo-immunotherapy and some of the newer treatments may cause the following, listed below. You are unlikely to have all of these, and for most people, the side effects aren’t severe and stop when treatment stops. There are medicines you can take to alleviate these symptoms. Ask for advice from your medical team.

Clinical Trials

You may have heard about clinical trials, and when you need treatment, it may be something you wish to consider. This section explains what these are and why they may be right for you.

What is a clinical trial?

Clinical trials are planned studies involving patients. In CLL, the studies are usually testing new drugs, typically comparing them with existing treatments in order to find better therapies. Trials are essential for evaluating new treatments.

What are the different types of clinical trials?

There are three types of clinical trial, phase 1, phase 2 and phase 3. Each new drug treatment must go through all phases.

Phase 1 trials are concerned with safety, optimum dosage and frequency, and side effects.

Phase 2 trials try to find out what measurable effect the new drug may have on the disease.

Phase 3 trials compare new treatments with the best currently available treatment (standard treatment).

What is a randomised clinical trial?

Most phase 3 trials are randomised. That is, patients who enter the trial are allocated to one of two or more planned treatments, usually by computer. Each group of patients in the trial will have a treatment which is effective against CLL, and the object is to see how well each treatment performs against the others.

How are clinical trials planned?

Clinical trials are very closely controlled, and doctors are required to write a detailed plan of how the trial will proceed. This is then reviewed by independent bodies of experts to ensure that the trial meets all of the strict criteria before it can go ahead.

Are there advantages in being in a clinical trial?

The main advantages of being in a trial are:

Is a clinical trial right for me?

Your consultant will advise you if you are suitable to consider a trial. There are usually certain pre-conditions that mean that not all patients qualify. If you have other health problems apart from CLL, you could be excluded, depending on their nature and severity. You may also be excluded because of age limitations, depending on the nature of the trial. However, there are usually several CLL trials running at any one time, and you may well qualify for one of them. Before entering a trial, you would have a thorough check-up, which may include scans and heart checks.

How do I find a clinical trial?

Your CLL consultant will have all the information on the trials that are currently recruiting patients and will be able to advise if you would qualify. You can also find information from the NHS at This will tell you if a trial is available in your local area. Clinical trials currently running in the UK can be found here. FLAIR is the major trial currently running in the UK. Up to date information can be found on the Cancer Research site here.

Finding a CLL specialist

It is important that you are seen by a haematology (blood) consultant who specialises in CLL. This is because treatment options, including trials, are developing quickly, and a CLL specialist will be in the best position to know about them.

Unfortunately, at present, there is no publicly available register of CLL specialists.

However, CLL specialists tend to work at a university (teaching) hospital. If you are being seen at a district general hospital (DGH) for your CLL, your consultant should be able to tell you the name of your regional teaching hospital. Your consultant will know the nearest specialist hospital for blood cancers, and where CLL clinical trials are being run in your area. If you want this information, don’t hesitate to ask your consultant for it. See also“How do I find a clinical trial?” advice above.

If you would like a second opinion about your diagnosis or treatment options, you are entitled to ask the hospital you attend for your CLL or ask your GP. The NHS states that you have a ‘right to be seen at a hospital / by a consultant of your choice’. As a general rule, it is best for all doctors involved in your care to be kept informed.

“Shared care” is another option. This involves being seen at a regional specialist centre in conjunction with local follow-up. This approach can ensure specialist input and access to trials, while most of your care remains local. There should always be close communication between the specialist centre, local team, GP and of course you.

To summarise: