Types of Treatment for Chronic Lymphocytic Leukemia

“Standard to care” refers to the best-known treatment. In cancer care, different doctors work together to bring out an overall treatment plan for the patient. This is called a multidisciplinary team. 

Treatments recommendations depend on many factors:

  • The size, grade and type of tumour
  • Whether the tumour is applying pressure on vital parts of the brain
  • If the tumour has increased to other parts of the body
  • Possible side effects
  • The patient’s preferences and overall health

Watch and wait for active surveillance for early-stage CLL.

Patients with symptoms or large amounts of CLL in the blood, spleen, or lymph nodes often need treatment soon after diagnosis. However, for other patients, immediate treatment is not required. It is suggested that the disease be monitored carefully without active treatment. This is the typical approach for patients with early-stage disease and no symptoms. This approach can be hard to understand, which is stressful. 

During this time, patients’ blood counts are watched closely, and physical examinations are performed regularly. If the CLL shows signs of worsening, active treatment would then start. Research studies showed no harm from the watch-and-wait approach, also called active surveillance or watchful waiting, compared with immediate treatment for early-stage CLL. Some patients don’t develop symptoms for years or even decades and will never need treatment. Patients whose blood counts did not change for several months or years may only need to be checked every 3 to 6 months.

Although most patients can live comfortably with CLL without active treatment, it is essential to use this time to improve overall health. This includes bringing all immunizations up to date and stopping smoking. However, patients having CLL should not receive the herpes zoster (shingles) vaccine because it can cause a shingles infection in patients with a lowered immune system.

Treatment is suggested for people with worsening blood counts who have also developed the symptoms. These symptoms might include increased night sweats, enlarged lymph nodes, fatigue, or lowered red blood cell or platelet counts. 

Chemotherapy 

Chemotherapy uses medicine to kill or stop the growth of cancerous cells. Depending upon the stage, different chemotherapy is given. The point that makes a difference is how the chemotherapy enters the body and which cells it affects.

A chemotherapy schedule usually consists of a certain number of cycles over a fixed period. A patient can be given one drug at a time or a combination of different drugs given simultaneously.

Chemotherapy uses drugs to destroy cancer cells, usually ending the cancer cells’ ability to grow and divide.

Common drugs for CLL include –

  • Bendamustine (Bendeka, Treanda)
  • Cyclophosphamide (Cytoxan)
  • Fludarabine (Fludara), most common for people with CLL who are younger and don’t have a deletion in chromosome 17
  • Chlorambucil (Leukeran)
  • Pentostatin (Nipent)
  • Cladribine (Leustatin)

The side effects of chemotherapy depend on the patient and the dose used. Still, they can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, and diarrhoea. These side effects usually go after treatment is completed.

Targeted Therapy

Targeted therapy aims at any factor contributing to the growth and development of cancer cells. It can be a specific protein, gene or tissue environment. This treatment blocks the growth and spread of tumour cells while limiting damage to healthy cells.

Targeted therapy for CLL includes –

  • Monoclonal antibodies – A monoclonal antibody recognizes and attaches to a specific protein in the surface of leukaemia cells, and it does not affect cells that do not have that protein. Monoclonal antibodies for CLL include-
    • Rituximab (Rituxan)
    • Obinutuzumab (Gazyva)
    • Ofatumumab (Arzerra)
    • Venetoclax (Venclexta)
  • Kinase inhibitors – Kinases are enzymes found in both healthy and cancer cells. Some cancer cells can be destroyed by drugs that block a specific kinase enzyme. Kinase inhibitors for CLL are relatively new and may only be available for patients with CLL that has returned or worsened (refractory CLL) or in clinical trials-
    • Idelalisib (Zydelig) is another type of kinase inhibitor given orally. It is also approved for treating recurrent CLL in combination with rituximab.
    • Ibrutinib (Imbruvica) is approved for people having CLL who have already received at least one other treatment. It is also approved as the first treatment for patients with a deletion in chromosome 17. However, it may cause bleeding and is not suggested for blood thinners patients.

The side effects of targeted therapy depend on the drug used. Mostly, a person’s first treatments with obinutuzumab, rituximab, or ofatumumab cause fevers and chills, which usually go after the first few treatments. Treatment with venetoclax can cause kidney failure and tumour lysis syndrome (TLS), a life-threatening medical emergency that could occur after treatment.

Combining systemic therapies

A treatment regimen usually consists of a specific number of cycles over a set period. Sometimes, a doctor may use a combination of drugs, but drugs are not always better than a single drug. When treatment begins, doctors may use several different drugs depending on the stage of the disease and the person’s age and health.

The combinations mentioned below can be used for CLL. Combinations including fludarabine are generally used for younger patients –

  • Cyclophosphamide, fludarabine and rituximab (called FCR)
  • Rituximab and fludarabine (sometimes abbreviated as FR)
  • Pentostatin, cyclophosphamide, and rituximab (called PCR)
  • Cyclophosphamide and fludarabine (called FC)
  • Idelalisib and rituximab for patients having recurrent CLL
  • Bendamustine and rituximab (called BR)
  • Obinutuzumab and chlorambucil for older patients
  • Ibrutinib, bendamustine, and rituximab for recurrent CLL

Stem cell Transplantation/Bone marrow Transplantation

A stem cell transplant is a medical process in which bone marrow that contains the cancer is replaced by highly specialized cells. These cells, known as hematopoietic stem cells, develop into the healthy bone marrow. Hematopoietic stem cells are the blood-forming cells found in the bloodstream and the bone marrow. These stem cells form all of the healthy cells in the blood. Presently, this procedure is more commonly called a stem cell transplant than a bone marrow transplant because it is the stem cells in the blood typically being transplanted, not the actual bone marrow tissue.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cells – autologous (AUTO) and allogeneic (ALLO). AUTO uses the patient’s stem cells, while ALLO uses donated stem cells. In both types, the target is to destroy all cancer cells in the blood, marrow, and other body parts using high doses of chemotherapy or radiation therapy and then allow replacement blood stem cells to create healthy bone marrow.

Side effects depend on the child’s general health, the type of transplant, and other factors.

Radiation Therapy

Radiation therapy uses high-energy X-rays or particles to destroy cancer cells. The most common radiation treatment type is external-beam radiation therapy, in which radiation is given from the machine outside the body. Radiation therapy is not often used to treat CLL because the disease is present throughout the body. However, radiation therapy can be beneficial to shrink an enlarged spleen or swollen lymph nodes and relieve specific symptoms.

Side effects from radiation therapy can include mild skin reactions, upset stomach, fatigue, and loose bowel movements. Most side effects go soon after treatment is completed. 

Surgery

Sometimes, surgery to remove the spleen, known as splenectomy, may be suggested because the spleen can become very enlarged in a person having CLL. 

Before surgery, talk to the health care team about the possible side effects of the specific surgery.

Palliative Care 

Cancer and its treatment have side effects that can be mental, physical or financial and managing the effects are palliative or supportive care.

Palliative care includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies. 

Palliative care focuses on alleviating how you feel during treatment by managing symptoms and supporting patients and their families with other non-medical needs. Regardless of type and stage of Cancer age, any person may receive this type of care.

Palliative treatments for CLL may include –

  • Immunoglobulin for infections that keep coming back. Giving IV each month can be helpful because people with CLL have fewer normal antibodies to help them fight infections.
  • Rituximab can also be helpful if the patient’s immune system makes antibodies against the body’s blood cells. 
  • High doses of corticosteroids help the body stop forming antibodies that destroy red blood cells or platelets.
  • A splenectomy for patients who make antibodies against their healthy blood cells.

Refractory CLL

If leukaemia does not respond to treatment, the disease is called refractory. If CLL becomes resistant to 1 drug, the drug no longer works; other treatments or drugs are often recommended. Palliative care will also be essential to help relieve symptoms and side effects.

For many people, a diagnosis of refractory CLL is very stressful and difficult to bear. 

Remission

Treatment aims to relieve symptoms from CLL and reduce the quantity of remaining CLL as much as possible. A complete remission (CR) happens when the doctor cannot find evidence of remaining leukaemia after continuous testing. A partial remission (PR) is when there is some leukaemia remaining.

A PR is most common for CLL people who receive the current standard treatments. With a PR, patients can feel well with normal blood counts, have no swollen spleen or lymph nodes, and have noticeable amounts of CLL in the bone marrow.

New monitoring methods, known as minimal residual disease (MRD) methods, can better find fewer abnormal lymphocytes and differentiate between healthy and abnormal lymphocytes. MRD methods are now being used often to determine the depth of remission in patients with CLL.

The aim of newer, more intensive treatments or targeted therapies is to kill more cancer cells in the hope of extending a person’s life. In the future, the definition of complete remission in CLL is likely to change with advancements in technology. For instance, some sensitive tests can find minimal abnormal DNA changes specific to CLL levels. When these sensitive tests can not find any CLL, it is called molecular remission.

Remission and chance of recurrence

When cancer can’t be detected in the body and there are no symptoms, this is known as remission. This may be called having ‘no evidence of disease’.

A remission can be temporary or permanent. Many people worry about the recurrence of cancer.

Finding a CLL recurrence doesn’t mean that treatment is needed right away. The watch-and-wait approach is usually recommended, with active treatment beginning only if the disease causes symptoms again.

If treatment doesn’t work

If cancer can’t be treated or controlled, it leads to advanced or terminal cancer. It is vital to have straightforward conversations with your health care team to express your feelings, preferences, and concerns. The health care team has unique skills, knowledge, and experience to assist patients and their families. Ensuring that a person is physically comfortable, free from pain, and emotionally supported is extremely important.