Exciting Advances in the Treatment of Patients with Chronic Lymphocytic Leukemia

New therapies that are now available for people with this type of cancer have fewer side effects than traditional chemotherapy and can improve survival and quality of life.
June 2018 Vol 4 No 3
Kristen Chanley

Leukemia is a cancer in the blood and the bone marrow. It is divided into 4 major types based on the characteristics of these types, including acute lymphocytic leukemia (ALL); acute myeloid leukemia (AML); chronic lymphocytic leukemia (CLL); and chronic myeloid leukemia (CML).

About 60,000 Americans will be diagnosed with leukemia this year, and more than one-third of them will have CLL—the most common type of leukemia in adults.1 Both ALL and CLL start in white blood cells called “lymphocytes,” but they behave in different ways and respond to different treatments.

Unlike acute leukemia (such as ALL or AML), which progresses quickly, CLL typically progresses more slowly and may not require immediate treatment. However, chronic leukemia, such as CLL and CML, can be harder to cure than acute leukemia. New treatments for CLL can now be used with fewer side effects than traditional chemotherapy and can improve the patient’s health outcomes and quality of life.

Recognizing CLL Can Be a Challenge

People with CLL usually don’t have specific symptoms. In fact, CLL is usually suspected and diagnosed after routine blood work shows elevated levels of lymphocytes. In some cases, people with undiagnosed CLL may have a poorly functioning immune system, leading to infection or CLL cells in the bone marrow, causing anemia or a low number of platelets. These symptoms may eventually lead to the diagnosis of CLL.

For patients who do experience symptoms of CLL, the most common symptom is swollen lymph nodes (or glands) in the neck, underarms, or groin. Additional symptoms include discomfort from an enlarged spleen, fever, chills, night sweats, weight loss, recurring infections, and abnormal bleeding.2 Once CLL is suspected, patients often have a bone marrow test, which involves collecting 2 different samples—the bone marrow aspirate (the soft-tissue inside the bone) and the bone marrow biopsy (bone marrow tissue, including the bone).

According to Gwen Nichols, MD, Chief Medical Officer for the Leukemia & Lymphoma Society (LLS), this evaluation is extremely important, because it confirms the diagnosis and allows for more advanced molecular tests to be performed. The flow cytometry test, also known as immunophenotyping, is the standard test performed on the bone marrow aspirate to confirm the diagnosis of CLL.

“An increase in lymphocytes could mean CLL, or it could be a sign of an infection. Unfortunately, under the microscope, without the benefit of special pathologic tests like flow cytometry, errors can be made,” Dr. Nichols explained in an interview with CONQUER magazine. “Flow cytometry will tell you if those cells are all the same kind of lymphocytes, if they are clones, and if those lymphocytes have the typical markers of CLL,” she added.

Most (more than 95%) patients with CLL have B-cell CLL—the less aggressive of the 2 types of CLL. Only about 1% of patients have T-cell chronic leukemia, such as T-cell prolymphocytic leukemia.2

Genetic Testing

Once CLL is diagnosed, patients have the option of getting genetic testing to learn about their specific subtype of CLL.

“These tests really matter when dealing with CLL. In the past, if you were diagnosed with CLL, you were either given the standard ‘cocktail’ [of chemotherapy drugs], or you would be advised to watch and wait,” Dr. Nichols said. “That isn’t the case anymore. These newer tests might help you to get a therapy specific to your individual disease. Patients need to be proactive and ask questions about some of the common mutations we see in CLL.”

Many biomarkers (biologic markers) and gene mutations (changes) have been identified that indicate the prognosis of the CLL for each patient, and whether particular treatments will be effective.

According to the LLS, the specific biomarkers in CLL include:

  • Blood markers, such as B2M
  • Genetic markers, including the IGHV gene mutation
  • Genetic abnormalities detected by tests such as FISH or metaphase cytogenetics, particularly chromosome 17p deletions, which indicate abnormalities in the TP53 gene and a poor response to chemotherapy
  • Protein markers, such as ZAP-70, CD38, or CD49d.

“Genetic testing, and the information derived from these tests, helps patients make life choices about their treatment,” Dr. Nichols said. “There are patients who shouldn’t be treated with standard of care, because they have a small chance of responding, but you won’t know that if you don’t get tested. I urge patients to research the important tests for CLL (available at and take that information and talk to their doctors.”

Treatment Tips

Because CLL is a chronic disease that progresses slowly, one treatment option is to watch and wait. Although this approach can be difficult for some patients, Dr. Nichols says that it is an important option, because all treatments have side effects (toxicity), and the more treatments used, the less effective they become.

“The treatments have toxicity, and if we knew they were curative, it would be an easy decision to have the treatment. It’s important to understand that every time you treat something, it gets tougher to treat it the next time, so you want to be sure it requires treatment,” advises Dr. Nichols.

If treatment is required, standard treatment approaches for patients with CLL include chemotherapy, radiation, and drug therapy, including monoclonal antibodies and targeted drugs.

Current Treatments

Several chemotherapy drugs are used for patients with CLL, including fludarabine, chlorambucil, cyclophosphamide, and bendamustine hydrochloride.

In the past decade, several new drugs have been approved by the FDA for patients with CLL. These include immunotherapies called monoclonal antibodies, as well as several targeted therapies that target specific markers in CLL.

The monoclonal antibodies approved for CLL may be used in disease that has relapsed (came back) after chemotherapy, and some are used together with chemotherapy. These drugs include Arzerra (ofatumumab), Campath (alemtuzumab), Gazyva (obinutuzumab), Rituxan (rituximab), and Rituxan Hycela (rituximab and hyaluronidase human). Of these newer therapies, Arzerra, Gazyva, and Rituxan Hycela can be used as the first treatment for patients with CLL, in addition to patients with relapsed disease.

The targeted therapies that are currently approved for CLL include Imbruvica (ibrutinib), which is used in patients with or without 17p deletion; Venclexta (venetoclax), which is used for those with relapsed CLL and 17p deletion; and Zydelig (idelalisib), in combination with Rituxan, for patients with relapsed CLL.

“There are a lot of reasons to be hopeful, because there are so many options available now for patients with CLL that are not just traditional chemotherapy options. The fact that there are approved options is very exciting, and even though they are not necessarily curative right now, they will likely give patients long periods of good health,” Dr. Nichols said.

“And for the other exciting options that may currently only be second or third line, CLL patients have time so that we can keep working on them,” she added.

Clinical Trials

Dr. Nichols urges patients to consider a clinical trial as another treatment option that may allow them to try a new therapy in development. “If more patients participate in clinical trials, this will help move new therapies forward to a world where chemotherapy becomes a much later option,” she said.

For patients who are considering a clinical trial, LLS has a Clinical Trial Support Center (CTSC) staffed by specially trained nurses who help patients enroll in clinical trials based on very individualized assessments. For more information, or to be connected to a CTSC nurse, call an LLS Information Specialist, at 800-955-4572.


1. American Cancer Society. Key statistics for chronic lymphocytic leukemia. Updated May 10, 2018.
2. American Society of Clinical Oncology. Leukemia - chronic lymphocytic - CLL: symptoms and signs.
3. Leukemia & Lymphoma Society. CLL staging.

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Last modified: August 16, 2018

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