Treatment options for chronic lymphocytic leukaemia (CLL)

A team of health professionals decides if you need treatment straight away. They also decide what treatment options you have.

In recent years, doctors have developed many new treatments for chronic lymphocytic leukaemia (CLL). They no longer use chemotherapy as the main treatment for CLL. The most common treatments for CLL are targeted cancer drugs . 

The decision about treatment is made by you and your healthcare team together. There might be different options. You might have to think about if you would prefer:

• a tablet that you take every day

• a course of treatment for a certain amount of time, such as a few months. And then time off treatment.

Deciding which treatment you need

A team of doctors, and other professionals discuss the best treatment and care for you. They are the multidisciplinary team (MDT). Your MDT might include:

• a haematologist - a doctor specialising in blood cancers
• a haemato-pathologist – a doctor who examines bone marrow or lymph node biopsies
• a radiologist – a doctor specialising in reporting x-rays and scans
• a specialist haematology nurse – also called a clinical nurse specialist (CNS)
• a palliative care doctor - a doctor specialising in controlling cancer symptoms

You may not need treatment straight away. Your team decides whether you need treatment depending on your:

• symptoms
• stage of CLL
• the results of certain blood tests and if the results have changed over time

Everybody who has CLL should have the diagnosis confirmed by a specialist at the hospital. But in some cases, the GP will lead the care of your CLL. This might be the case if, for example, you are diagnosed during a routine blood test for something else.  

If you need treatment, your team plans it depending on:

• whether there is a change (mutation) in the TP53 gene
• your general health and level of fitness 
• personal wishes

Your doctor will talk to you about your treatment options. They will discuss the benefits and the possible side effects with you.

The main treatments

You are likely to have a targeted cancer drug. You might have the drug on its own or together with another targeted or immunotherapy drug.

The main aim of treatment is to control your cancer and get you into remission. Remission means there's no sign of active leukaemia in your body. And you don’t have any symptoms. You may then have a period where you do not need any treatment. This remission can last for years.

Targeted cancer drugs

Targeted cancer drugs can change the way that cells work and help the body control the growth of cancer. There are different types for CLL. The 2 main types are:

• Bruton Tyrosine Kinase Inhibitors (BTKi), such as ibrutinib and acalabrutinib
• B-cell lymphoma inhibitors (Bcl2) such as venetoclax

Some targeted drugs are also a type of immunotherapy. These are called monoclonal antibodies (MABs). Rituximab and obinutuzumab are examples of MABs for CLL. If you have these drugs with chemotherapy, this is called chemoimmunotherapy.

Chemotherapy

Chemotherapy uses anti cancer (cytotoxic) drugs to destroy cancer cells. The drugs circulate throughout the body in your bloodstream. Doctors don't often use chemotherapy for CLL any more.

Treatment stages

There are several stages of treatment for CLL. These are:

• watch and wait
• first line treatment
• treatment when CLL comes back

Watch and wait

Your doctor might decide not to give treatment if you don't have any symptoms and your CLL is at an early stage. Instead, they keep a close eye on you. You might hear this called watch and wait.

Your doctor chooses to do this because you have no symptoms bothering you and your CLL can be very slow growing. At the moment there isn’t any evidence to show that treatment helps people in this situation.

Your GP or haematologist will keep a close eye on you and check your blood cell count. They are looking for any changes in your CLL. You start treatment if your CLL gets worse or you develop symptoms.

It can be difficult to cope with not having treatment especially when you have been told you have leukaemia.  

First line treatment

This is your first treatment. Your doctor might offer you treatment if you have symptoms, or if your CLL is at a more advanced stage.

The treatment may get your CLL under control (in remission). You may then have a period where you do not need any treatment. This remission can last for years.

The treatment you have depends on whether your CLL has a change (mutation) in the TP53 gene.

If your CLL doesn’t have a change (mutation) in the TP53 gene

You might have:

• a targeted drug on its own, such as acalabrutinib or zanubrutinib
• venetoclax and obinutuzumab
• venetoclax and ibrutinib

It isn't common to have chemotherapy as your first treatment. If you do have chemotherapy, you usually have it together with a type of targeted immunotherapy drug. This is called chemoimmunotherapy. The combination is likely to be fludarabine, cyclophosphamide and rituximab (FCR).

You might not be fit enough to have one of these treatments. If this is the case, you can have chlorambucil chemotherapy tablets on their own, or steroids. You can take these at home.

If your CLL has a change (mutation) in the TP53 gene

You usually have treatment with targeted cancer drugs such as:

• acalabrutinib or zanubrutinib
• venetoclax and obinutuzumab
• ibrutinib
• venetoclax and ibrutinib
• idelalisib and rituximab

Treatment when CLL comes back

CLL tends to come back after a period of time. This is called a relapse. You might need more treatment if this happens. But some people don’t need treatment straight away. The next lot of treatment you have is called second line treatment.

Many people with CLL can have further remissions with more treatment. The remissions tend to get shorter, the more treatment you have.

Your doctors consider many factors when deciding about your treatment. There are lots of different options for second line treatment. These include:

• acalabrutinib or zanubrutinib
• venetoclax on its own, or with rituximab
• idelalisib and rituximab
• ibrutinib

Other treatments

Other treatments you might have for CLL include:

• stem cell transplant
• radiotherapy to your spleen
• surgery to your spleen
• steroids
• supportive treatments such as antibiotics, blood products or steroids

Clinical trials

Your doctor might ask if you’d like to take part in a clinical trial. Doctors and researchers do trials to make existing treatments better. And to develop new treatments.