CD20 Marker in Lymphoma: Role, Treatments, and What Patients Need to Know

CD20 is a protein that helps doctors diagnose and treat many types of lymphoma. Understanding what CD20 is and its significance can help you feel more confident about your treatment options.

CD20 is a protein found on the surface of most B cells, explained Erev Tubb, MD, medical oncologist, hematologist, and medical director of the Leading-Edge Cancer Center at Inspira Medical Center Mullica Hill in southern New Jersey. “These B cells are a type of white blood cell that plays an important role in the immune system.”

CD20 acts as a marker that helps distinguish B cells from other cells in the body. When B cells turn cancerous and develop into lymphoma, they typically still express CD20 on their surface. This makes CD20 very useful for diagnosing and treating many B-cell lymphomas.

The presence of CD20 on lymphoma cells gives doctors a specific target for treatment, Dr. Tubb said. “Several therapies, including monoclonal antibodies such as rituximab, are designed to attach to the CD20 protein and destroy those lymphoma cells. In short, CD20 helps doctors identify and treat certain lymphomas more effectively.”

Targeted treatments like these can lead to improved response and fewer side effects than traditional chemotherapy, which affects many healthy cells along with cancer cells.

Testing for CD20 is a standard part of the diagnostic workup when lymphoma is suspected. Your doctor performs this test using tissue from a biopsy (tissue sample). “Pathologists use a laboratory technique called immunohistochemistry (IHC) to detect whether the CD20 protein is present on the surface of lymphoma cells,” Dr. Tubb explained.

This test gives your doctor three important pieces of information:

• Whether CD20 is present on your lymphoma cells

• How strongly the protein is expressed

• Whether you may benefit from CD20-targeted treatments

In some cases, your doctor may order additional testing, such as flow cytometry. This test uses lasers to analyze the cells for the presence of specific proteins on their surfaces. Flow cytometry is especially helpful when lymphoma cells are circulating in your blood or when doctors need a more detailed assessment of CD20 expression.

Since CD20 is not found on most other cells in your body, treatments that target CD20 can attack cancer cells more directly and usually cause fewer side effects than traditional chemotherapy.

Daniel Landau, MD, oncologist at the Medical University of South Carolina in Charleston, explained how these targeted therapies work. “The way our body fights viruses or bacteria is to create what’s known as an antibody. Sort of like a little protein that floats around the body looking for something it recognizes to stick to. And when it finds that thing, it sticks to it, and that tells the rest of our immune system to attack.”

This same concept is used in targeted therapies to identify and target cancer cells while sparing healthy cells.

“CD20 expression is found in nearly all B-cell lymphomas, including diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma,” Dr. Tubb said. “However, the amount of CD20 on the surface can vary, which may influence how well CD20-targeted therapies work.”

Diffuse Large B-Cell Lymphoma (DLBCL)

DLBCL, the most common type of non-Hodgkin lymphoma, typically shows strong CD20 expression. This makes it highly responsive to CD20-targeted therapies, which have become a cornerstone of treatment for this aggressive lymphoma.

Follicular Lymphoma

Follicular lymphoma cells almost always have CD20 on their surface. This type of lymphoma grows slowly and usually responds well to anti-CD20 therapy. Your doctor may recommend these targeted therapies on their own or in combination with chemotherapy.

Mantle Cell Lymphoma (MCL)

Mantle cell lymphoma is characterized by strong expression of CD20. First-line treatment for MCL often includes CD20-targeted therapies combined with chemotherapy. Two of the most common regimens are R-CHOP and BR:

• R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

• BR: bendamustine and rituximab

Chronic Lymphocytic Leukemia (CLL)

While technically a leukemia, CLL shares many characteristics with lymphoma and typically expresses CD20, though sometimes at lower levels than other B-cell malignancies.

CLL is often a slow-growing disease and may initially not require treatment. Instead, it is closely monitored by a healthcare provider. However, as it progresses, treatment options include targeted therapies, chemotherapies, and/or immunotherapies.

CD20-targeted therapies work by binding to the CD20 protein on the surface of B cells and directing the immune system to attack and destroy these cells. This can slow or stop the progression of CLL and other B-cell lymphomas. Your doctor may recommend CD20-targeted therapies alone or in combination with other treatments.

Monoclonal Antibodies (e.g., Rituximab)

“Monoclonal antibodies are man-made antibodies designed to target what we want to trigger an immune response against,” Dr. Landau explained. Rituximab (Rituxan) is the first CD20-targeted therapy approved for the treatment of lymphoma.

“Rituxan sticks to CD20, and the rest of the immune system then comes in and attacks lymphoma cells,” Dr. Landau said. When rituximab attaches to the CD20 protein on lymphoma cells, it triggers several mechanisms that lead to cancer cell death:

• Direct cell death signaling

• Marking cells for destruction by other immune cells

• Activating immune system proteins that punch holes in cancer cells

Other CD20-targeted monoclonal antibodies include obinutuzumab (Gazyva) and ofatumumab (Arzerra), which may work slightly differently or be more effective in certain situations.

Bispecific Antibodies and Emerging Therapies

Newer treatments called bispecific antibodies work differently from traditional monoclonal antibodies. “I explain bispecific antibodies as Y-shaped molecules where one half binds to a CD marker and the other half binds to an immune cell, then essentially shoves them together,” Dr. Landau said.

By simultaneously binding to both CD20 on cancer cells and CD3 on immune T cells, bispecific antibodies bring these cells into direct contact, enabling your immune system to destroy lymphoma cells more effectively. Several bispecific antibodies are now approved or being studied in clinical trials for various types of lymphoma.

While most B-cell lymphomas express CD20, most T-cell lymphomas do not. In addition, certain rare types of B-cell lymphoma, such as plasmablastic lymphomas, also do not express the marker, Dr. Tubb noted. “Knowing whether a lymphoma expresses CD20 helps oncologists choose the most appropriate and effective therapy for each individual patient.”

Dr. Landau added that some lymphomas “have different targets (like CD30), and there are specific treatments for this as well (brentuximab, for example). This is common in Hodgkin lymphoma, for example.”

In some cases, lymphoma cells may lose CD20 expression during treatment or when the cancer comes back (recurrence). This typically occurs because the cancer cells adapt to avoid being targeted by CD20-focused therapies. If this happens, your doctor will look for other markers on the cancer cells and may recommend treatments that don’t target CD20.

Researchers are continually seeking more effective ways to target CD20 and improve treatment outcomes. Some new approaches include:

• More potent antibodies that trigger stronger immune responses

• Antibody-drug conjugates that deliver chemotherapy directly to CD20-positive cells

• Novel bispecific antibodies with improved efficacy and safety profiles

• CAR T-cell therapies that engineer your own immune cells to recognize CD20

• As doctors discover more about the role of CD20, they’re able to personalize treatment plans in new ways to help people with lymphoma live longer, such as:

• Predicting treatment response by measuring the amount of CD20 on your lymphoma cells

• Monitoring CD20 levels during treatment to make more informed treatment decisions

• Combining CD20-targeted therapies with other treatments to improve outcomes

• Determining who will benefit most from specific CD20-targeted approaches

If your lymphoma tests positive for CD20 expression, you may be a candidate for targeted therapies. During the diagnostic workup, your doctor will test your lymphoma cells for the presence of CD20. Most B-cell lymphomas express CD20, allowing them to be treated with targeted therapies such as rituximab and newer bispecific antibodies.

CD20-targeted treatments have helped many people with lymphoma, but they are not right for everyone. Some lymphomas do not express CD20, and cancer cells may lose this marker over time. Your oncologist will determine the best treatment for you based on the type of lymphoma you have and its characteristics.