Chronic Lymphocytic Leukemia (CLL)

CLL (Chronic Lymphocytic Leukaemia) in brief

Chronic lymphocytic leukaemia is one of the most common blood cancers in older people. In Germany, around 4,000 to 5,000 people are diagnosed each year. The average age at diagnosis is about 70 years.

The condition should not be equated with an acute leukaemia. CLL progresses only slowly.

CLL in numbers

New diagnoses per year

approx. 4,000 to 5,000 in Germany

Typical age at diagnosis

about 70 years

Course

slowly progressing

Below you will find further information about CLL.

What lies behind the word leukaemia?

Leukaemia translates literally as „white blood". Rudolf Virchow first described the condition and observed in affected patients a reduced proportion of red blood alongside a markedly increased proportion of white blood.

What exactly is CLL?

In CLL, the B lymphocytes are affected. These are a special group of white blood cells. Healthy B lymphocytes form a wide variety of antibodies and thereby protect our body against viruses and bacteria.

To produce the billions of different antibodies, new B lymphocytes are constantly being formed and trained against the many pathogens. During this frequent formation, genetic mutations also arise again and again. Most of these cells then die off. Depending on the gene mutation, however, a growth advantage can rarely occur. The cells divide more frequently than others. They multiply in an uncontrolled way. Over time they can also displace the healthy cells – and this is when we speak of CLL.

Why do I have CLL?

The exact factors that lead to the development of CLL are still not established.

Confirmed risk factors are:

• The organic solvent benzene is associated with an increased risk of developing CLL.
• There is also an increased risk if first-degree relatives have had CLL.

Symptoms of CLL

CLL is often discovered by chance on the basis of elevated white blood cells during a blood test, without the affected person necessarily having any symptoms.

Otherwise, the classic symptoms include:

• Swelling of lymph nodes
• General weakness
• Fever
• Night sweats
• Weight loss
• „Poor blood counts" (anaemia, or a drop in the blood platelets responsible for clotting)
• Frequent infections

When is CLL treated?

CLL is a slowly progressing condition. Whether treatment is required depends on the patient's symptoms and the stage of the disease.

Staging

Staging is carried out according to Binet in 3 groups:

• A – early stage: at most 2 enlarged lymph nodes, good blood counts
• B – intermediate stage: at least 3 enlarged lymph node regions, good blood counts
• C – advanced stage: poor blood counts

No treatment needed

If you have no complaints yourself, it is often possible simply to observe the disease. This is referred to as a „watch and wait" approach. It usually applies in stages A and B. As a rule, regular checks of the blood and lymph nodes are then carried out at the doctor every 3 to 6 months.

This approach was most recently confirmed by a placebo-controlled study in patients at higher risk of CLL progression (the CLL12 study). Here, continuous treatment with a tablet therapy (ibrutinib) was compared with a sugar tablet. It was shown that immediate treatment does not lead to prolonged survival – that is, patients in both groups lived equally long.

Treatment needed

Treatment is required in the following situations:

• Poor blood counts (= Binet stage C)
• Symptoms (fever, night sweats, weight loss)
• Severe tiredness, exhaustion (fatigue)
• Very enlarged spleen (clearly palpable below the rib cage)
• Very large lymph nodes (over 10 cm)

How is CLL treated?

Over the past 10 years, the way CLL is treated has changed completely. In the past, chemotherapy was the treatment of choice for CLL. Today, CLL is first examined for certain molecular markers. Depending on the marker, a tailored therapy then follows.

Today, certain antibodies and tablets form the backbone of treatment. The antibodies bind to a specific surface marker on the CLL cells that is highly characteristic of these cells. Antibodies are administered either into the vein or into the subcutaneous fat. The various tablet-form medicines block signalling pathways in the CLL cells that they need in order to grow.

Depending on the choice of therapy, it is either time-limited or a continuous treatment.

How exactly were clinical trials able to change the treatment landscape in CLL?

To test new medicines, they go through several phases. Only phase III trials serve to verify whether a new medicine is really better than the previous standard.

In CLL, Resonate-2 was one such trial. It enrolled 269 patients. For each patient, „by lot" (randomisation) determined whether they were assigned to the chemotherapy arm (chlorambucil) or to the arm with the new medicine (ibrutinib). The patients were then monitored at regular intervals.

Looking at the survival curves of the two arms after 27 months, considerably more patients were alive in the ibrutinib treatment arm after 27 months. It is trials like these that drive progress in medicine.