Chronic Lymphocytic Leukaemia Recurrent

When chronic lymphocytic leukaemia returns after treatment, it is called a relapse. While the condition is not usually curable, treatment can control it, and many people experience long periods of remission before the disease comes back again.

Table of contents

• What is recurrent chronic lymphocytic leukaemia
• Deciding about treatment when CLL comes back
• Treatment options for relapsed CLL
• How you have treatment
• How does treatment work
• After first relapse

What is recurrent chronic lymphocytic leukaemia

When chronic lymphocytic leukaemia comes back after treatment, it is called a relapse or recurrent disease. A relapsed patient is defined as one who has previously achieved complete remission or partial remission, but who exhibits evidence of disease progression after a period of 6 months or more^[12]. Often the leukaemia relapses slowly, so you may not need further treatment straight away^[5].

During the course of the disease, you might have several relapses. The aim of treatment is to get your CLL under control. When there is no sign of active leukaemia in your body, the CLL is said to be in remission. CLL is not usually curable, but treatment can control it^[5].

Even in complete remission, a few CLL cells may remain, which makes the cancer likely to come back. However, it may be a while before that happens since CLL can be slow-growing. Some people live for years after their CLL diagnosis before they need treatment. Others experience post-treatment remission that lasts for years^[17].

Deciding about treatment when CLL comes back

You might not need further treatment straight away. But your doctor might suggest treatment if you have symptoms. When you relapse, your treatment plan depends on several important factors^[5]:

• How long your CLL has been in remission
• The treatment you had before
• How well the treatments you have had worked
• Whether the leukaemia cells have a change (mutation) in the TP53 gene
• Your general health and fitness
• Your personal wishes

Your doctors will repeat tests to see if your leukaemia cells have changes (mutations) in the TP53 gene. This is because these genes can change over time. Most treatments have side effects and some drugs might be more suitable for you than others. Your doctor will decide which drug is best for you, to lower the risk of treatment complications^[5].

Your doctor will discuss your options with you. They will tell you about the different treatment side effects. They will also discuss what each treatment involves, for example, how long you have it and how often you will need to go to the hospital^[5].

Treatment options for relapsed CLL

The first time your CLL comes back it is called a first relapse. Some people have a long period of remission before their CLL comes back. In this situation you might have the same drugs you had as your first treatment. Or, you might get a different drug or combination of drugs^[5].

Some of the common treatment options for relapsed CLL include^[5]:

• Acalabrutinib
• Venetoclax on its own, or with rituximab
• Idelalisib and rituximab
• Ibrutinib
• Zanubrutinib

If you have relapsed or refractory CLL that has a 17p chromosome deletion (the short arm “p” of chromosome 17 is missing) or a TP53 gene mutation, treatment is usually targeted therapy. The most common targeted therapy drugs offered are ibrutinib, acalabrutinib, zanubrutinib, venetoclax, or a combination of venetoclax and rituximab^[11].

Your doctor might suggest a stem cell transplant, although this is not a common treatment for CLL. Your doctor is most likely to suggest this if you are young and well enough to tolerate the intensive treatment. And if your leukaemia has come back quite quickly after your first treatment^[5].

How you have treatment

Most people have treatment as an outpatient. Treatment can be^[5]:

• Tablets
• An injection into a vein as a drip (intravenously)

You have treatment in cycles or blocks. Each cycle usually lasts for 28 days. You have some drugs every day and others weekly or less often. After each cycle of treatment, your team will check your side effects. They will also check how well treatment is working. You might have up to 6 cycles of treatment. But some treatments carry on until they stop working^[5].

How does treatment work

Cancer cells have changes in their genes (DNA) that make them different from normal cells. These changes mean that they behave differently. Cancer cells can grow faster than normal cells and sometimes spread^[5].

Targeted cancer drugs work by ‘targeting’ these differences that a cancer cell has. They work in different ways. For example, they can^[5]:

• Stop cancer cells from dividing and growing
• Encourage the immune system to attack cancer cells
• Stop cancers from growing blood vessels

After first relapse

When CLL comes back again, it is called a second relapse, third relapse, and so on. You might have one of the other treatment options mentioned above. You might have other drugs as part of a clinical trial if you have already had 2 or more treatments^[5].

Relapse may occur after a prolonged complete remission following initial treatment, or within months following a partial remission to second- or third-line treatment. Treatment of relapsed CLL often hinges on providing therapy that maximizes survival and disease control while minimizing toxicity with the overall goal of improving quality of life^[12].