How Chronic Lymphocytic Leukemia (CLL) Is Treated

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Treatment of chronic lymphocytic leukemia (CLL), one of four common types of leukemia, requires an individualized approach. Your medical team will present a variety of possible therapies to you—drugs like chemotherapy and monoclonal antibodies, radiation, stem cell transplantation, and others—and discuss what outcomes you can expect with each. In some cases, a watch-and-wait period (in which no treatment is given) may be appropriate instead.

At this time, no cure exists. Despite that, because of CLL's slow-growing nature, some people can live for years and even decades with it.

Any treatment for CLL is aimed at slowing disease progression and providing symptom relief, with hopes of achieving prolonged remission and good quality of life.

According to the American Cancer Society, your care team should consider your age and general health, as well as chromosomal abnormalities and the presence of certain immune cell proteins when determining the best course of CLL treatment. Testing can confirm the latter two factors.



Watching and Waiting

CLL progression is different in virtually every patient, so spontaneous remission and long periods with no symptoms can occur.

Patients who are not experiencing any symptoms of CLL such as night sweats, fevers, weight loss, anemia (a low red blood cell count), thrombocytopenia (low platelet counts), or frequent infections are not likely to benefit from treatment. Therapy at this stage in the disease will not prolong your life, nor will it slow down the progression of your leukemia. Therefore, a watch-and-wait approach is usually taken.

In a watch-and-wait situation, you will be followed by a hematologist or oncologist and will need to have blood work and be seen by your specialist every six to 12 months (or possibly more frequently).

Between visits, you will need to pay attention to signs that your cancer may be progressing. You may notice:

Many patients can remain on watch and wait for years before requiring treatment for their CLL. It can be very difficult to learn that you have cancer, then "wait for it to get worse" before you treat it.

While a period of watching and waiting can be hard, it's important to understand that it is the standard when CLL is not showing any symptoms. Research on this hasn't shown any benefit to starting treatment early.

Drug Therapies

When symptoms of CLL do occur, drug therapies are often the first-line treatment. A variety of medications and oral chemotherapy options exist for CLL patients.

B-Cell Receptor Inhibitors

Imbruvica (ibrutinib) is a once-daily oral medication (capsule or tablet) that has shown long-term effectiveness (five years+) for patients who have already been treated for CLL. Ibrutinib has subsequently been approved for front-line use in newly-diagnosed CLL patients as well.

Ibrutinib works against cancerous B lymphocytes, a type of white blood cell, by blocking Bruton’s tyrosine kinase (BTK)—an enzyme that promotes the survival of B leukocytes.

So far, the drug has been a potent weapon against CLL. In some research, ibrutinib has been shown to be more effective than chlorambucil, a chemotherapy treatment. One study achieved an overall response rate of 92%.

While tolerance is generally good, adverse side effects can include higher infection risk (neutropenia), hypertension, anemia, and pneumonia.

BCL2 Targeting Agents

Venclexta (venetoclax) is another oral medication approved for all adult cases of CLL. The drug has a positive safety profile and lower blood toxicity than other drugs in its class. Multiple studies have shown an overall response rate greater than 70%. 

Venetoclax selectively targets the specific B-cell lymphoma-2 (BCL2) by binding with proteins in BCL2 cells and promoting cell death. It does this while minimally affecting blood platelet counts.

Possible toxicities/side effects include tumor lysis syndrome, where rapid death of cancer cells overwhelms the kidneys' ability to clear byproducts (uric acid, potassium) from the blood. Neutropenia and pneumonia may also occur. Generally, if these problems arise, the treatment is paused and only resumed when they resolve.

Monoclonal Antibodies

Monoclonal antibodies are essentially artificial antibodies that attack a cancer. Whereas your immune system recognizes abnormal proteins on the surface of a bacteria or virus, these drugs "recognize" them on the surface of cancer cells.

Most types of monoclonal antibodies target the CD20 protein on type B lymphocytes. They include:

  • Arzerra (ofatumumab)
  • Gazyva (obinutuzumab)
  • Rituxan (rituximab)

Another monoclonal antibody, Campath (alemtuzumab), targets the CD52 protein and is used when initial therapies are ineffective.

Adverse side effects include allergic reaction, chest pain/racing heart, dizziness, infection risk, and tumor lysis syndrome.

Chemotherapy

For many years, oral chemotherapy with Leukeran (chlorambucil) was the standard of treatment for CLL once the cancer began to progress. While most patients did quite well on this therapy, it did not provide a complete response (CR) very often.

These days, chlorambucil is only used in patients who have other health concerns that prevent them from receiving stronger, more toxic chemotherapy.

Aside from Leukeran (chlorambucil), other common chemotherapy types include:

  • Fludara (fludarabine)
  • Nipent (pentostatin)
  • Leustatin (cladribine)
  • Treanda (bendamustine)
  • Cytoxan (cyclophosphamide)
  • Corticosteroids like prednisone

Side effects of chemotherapy include hair loss, nausea, mouth sores, and increased infection risk. Tumor lysis syndrome can also occur.

In some cases, CLL cells may be too concentrated in the bloodstream and cause circulation problems (leukostasis). Doctors may use a procedure known as leukapheresis to lower cancer cell counts immediately before chemotherapy is undertaken. In this procedure, blood is removed from the patient and cancer cells filtered out. The blood is then reintroduced to the patient. This can be an effective stopgap measure until chemotherapy has a chance to work.

Combination Therapies

It's common for oncologists to combine therapies depending on a patient's individual case.

One combination therapy proven effective is chemoimmunotherapy. For CLL treatment, it involves a mix of the chemotherapies fludarabine and cyclophosphamide along with the monoclonal antibody rituximab (collectively known as FCR).

Experimentation is ongoing to see if new combinations may work better than established treatments.

For example, a New England Journal of Medicine study of more than 500 CLL patients found that combination therapy of ibrutinib and rituximab may be more effective than FCR (a progression-free survival rate of 89% versus 73% at three years, and overall survival at 99% versus 92% at three years).

Your oncologist should be knowledgeable of established and emerging combination therapies that may work for your case.

Surgeries and Specialist-Driven Procedures

While some procedures for CLL may help slow disease progression, most are undergone to provide symptom relief.

Radiation Therapy

In patients with CLL, the use of radiation therapy is limited to providing symptom relief. It can be used to treat localized areas of swollen lymph nodes that cause discomfort or interfere with movement or function of nearby organs.

Stem Cell Transplant

In the case of other types of blood cancers, a great deal of research has been done to compare survival outcomes of patients who receive chemotherapy against stem cell transplant. Since the average age of a newly diagnosed CLL patient is between 65 and 70 years, typically too old to be considered a transplant candidate, these types of studies have not been done on this population. Meanwhile, 40% of CLL patients are under the age of 60 and 12% are under the age of 50.

Stem cell transplant may be an option for younger CLL patients with a poor prognosis.

Allogeneic stem cell transplant (transplant using donor stem cells) uses extremely high doses of chemotherapy to treat leukemia and donated stem cells to repopulate the patient’s immune system. The advantage of an allogeneic stem cell transplant is that, while it may be more toxic, it can cause a "graft-versus-leukemia" effect. That is, the donated stem cells recognize the leukemia cells as abnormal and attack them.

Even though these techniques are improving dramatically, there are still some major complications in 15% to 25% of patients, one being graft vs. host disease in which the donor tissue recognizes that patient's own healthy cells as foreign and launches an attack.

Currently, research to determine the role of non-myeloablative (a.k.a. "mini" transplants) in CLL is underway. Non-myeloablative transplants rely less on the toxicity of chemotherapy and more on the "graft-versus-leukemia" effect to treat cancer. This type of therapy may provide a treatment option for older individuals who would not be able to tolerate a standard allogeneic transplant.

Splenectomy

For patients experiencing an enlarged spleen as a result of the accumulation of CLL cells, splenectomy (surgical removal of the spleen) may initially help improve blood counts and relieve some discomfort. However, splenectomies for CLL are generally very rare.

One serious complication in fewer than 10% of CLL patients: The leukemia transforms into a more aggressive variety of the disease. In these rare cases, treatment plans can remain similar to CLL treatment or be completely revised to attack the more aggressive form. Your oncologist will guide you.

A Word From Verywell

At this time, while treatment for CLL may be able to provide patients with symptom relief and control of their leukemia, it can not provide a cure, and the course of the disease is extremely variable between different people. However, our understanding of this unique type of leukemia is constantly expanding. Research studies will continue to progress and potentially provide therapies with longer-term control or cure of CLL.

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