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CLL Treatment

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Updated 25.03.24

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?

In recent years there have been huge developments in new treatments and a move away from traditional chemotherapy. It is now extremely likely that your consultant will discuss the current treatment approaches with a form of targeted, small molecule therapy.

Targeted therapies for treatment of CLL can be broadly considered as either ‘Continuous’ treatment or a time limited ‘Fixed duration’ treatment. These different regimes contain different drugs or combinations of drugs. Both these approaches work extremely well and there may not be a right or wrong choice in your case.

Your consultant will help by advising you of the way each of these approaches will differ. For example, side effects may be different and the effect of the drugs on your body will need monitoring in different ways.

Choosing a treatment approach takes several factors into account. Firstly, and most importantly, is your general health and what specific health issues you have, for example, heart problems or chronic kidney problems. Secondly, there may be biological characteristics of your CLL which influence the choice. Additionally, taking into account what is important to you – you may have a preference.

It is important that both you and your consultant are comfortable with the decisions you make together. Before you decide, it is always sensible to discuss with someone at home as well as with your clinical nurse specialist.

A clinical trial may be an option for you. Your consultant will be able to provide you with further information. Please see the section below on Clinical Trials.

Treatments you may be offered include the following. The side effects and benefits of each treatment will be made as clear as possible by your medical team.

1. Fixed duration therapy

This is treatment which is given for a limited amount of time, and then stopped. You will still be closely monitored to make sure that your CLL does not return, and if this happens you may be restarted on the treatment.

Venetoclax with Obinutuzumab

This is used in first line treatment. Obinutuzumab is an antiCD20 antibody given as an intravenous infusion (also known as IV or ‘drip’). The antibody sticks to the surface of the CLL cells, killing off much of the circulating cells. Obinutuzumab is given for several weeks before starting venetoclax tablets. Venetoclax is a BCL2 look-alike. BCL2 is a protein which triggers a process in the CLL cells causing them to die off rapidly. The obinutuzumab monthly infusions will be completed after 6 months but the venetoclax tablets continue throughout.

The whole course of treatment lasts just over 12 months.

Venetoclax and Ibrutinib

This is another ‘frontline’ regime. It combines oral Ibrutinib, a BTK inhibitor with venetoclax. It is an entirely oral regime and lasts approximately 15 months.

Venetoclax and Rituximab

This can be given as a second (or more) line of treatment.

Rituximab is similar to obinutuzumab and is given intravenously. Venetoclax tablets start at the beginning of the regime and continue for 2 years. Once you are on the full dose of venetoclax you will start monthly doses of rituximab. After 6 doses of rituximab the venetoclax continues until the end of the 2-year course.


Traditional chemotherapy, usually known as FCR combines the chemotherapy tablets, fludarabine and cyclophosphamide with the antiCD20 monoclonal antibody, rituximab.

Because of side effects, this combination is much less used but for some people, particularly younger, fitter patients, has led to very long remissions.

2. Continuous therapy

This is treatment which continues until it stops becoming effective (relapses), or if side effects become too great. Different treatments may be considered if this occurs.

BTK inhibitor therapy: These are taken by mouth continuously and indefinitely. These drugs control CLL by isolating the cells from the vital chemical interactions which help sustain the CLL cells. By blocking a key intracellular pathway triggered by a receptor on the cell surface known as the B Cell Receptor, the CLL cells are unable to survive. This includes second generation drugs such as acalabrutinib and zanubrutinib as well as the longer established ibrutinib. These drugs can be given first line or later on after a venetoclax regime, for example.

Another B Cell Receptor pathway inhibitor, idelalisib, also taken by mouth as a continuous therapy, can be given for relapsed CLL. Idelalisib is usually combined with rituximab. It is used much less than BTK inhibitors but may have a role for some people.


Future therapies: There are new developments all the time which makes clinical trials very important in developing newer drugs and finding better combinations. BTKi, BCL2 type treatments, and monoclonal antibodies, will continue to be the cornerstone of frontline therapy in CLL for some time to come.

One area of research treating relapsed CLL is in the use of CAR-T cells. However, there are many challenges to this approach, and it is not yet established in CLL.

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 and CLARITY are the major trials currently running in the UK. There are several other trials, and up-to-date information can be found on the Cancer Research site here and on the UK CLL Forum 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. More information on your rights as a patient can be found on the NHS website here.

“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: