Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma, affecting thousands of people each year. Although it grows quickly, this aggressive blood cancer often responds well to treatment, and many people can be cured, especially when diagnosed and treated early.

Table of contents

• What is diffuse large B-cell lymphoma?
• Types and subtypes
• Signs and symptoms
• What causes DLBCL?
• Who is at higher risk?
• How is DLBCL diagnosed?
• Treatment options
• What to expect

What is diffuse large B-cell lymphoma?

Diffuse large B-cell lymphoma, commonly called DLBCL, is a type of cancer that affects the lymphatic system, which is the network of tissues, vessels, and organs that help your body fight infection^[1]. The lymphatic system includes lymph nodes, bone marrow, and other organs throughout your body^[1].

DLBCL is the most common type of non-Hodgkin lymphoma, a category of blood cancers that is separate from Hodgkin lymphoma^[1]. In the United States, DLBCL accounts for about 22 to 30 percent of all newly diagnosed cases of B-cell non-Hodgkin lymphoma^[3][8]. More than 18,000 people are diagnosed with this condition each year in the United States alone^[3].

This cancer develops in B cells, which are a type of white blood cell that normally makes antibodies to help fight infections^[2][3]. In DLBCL, healthy B cells change into fast-growing cancer cells. When doctors look at these cancer cells under a microscope, they appear larger than normal healthy B cells. The cancer cells spread out throughout the tissue in a scattered pattern, which is why doctors call them “diffuse”^[1].

DLBCL is considered an aggressive or fast-growing lymphoma^[3][11]. However, despite being aggressive, it is often treatable and sometimes curable, particularly when diagnosed early and treated right away^[1][2].

• Lymph nodes
• Bone marrow
• Gastrointestinal tract
• Central nervous system
• Skin
• Bones
• Thyroid
• Breast
• Brain

Types and subtypes

DLBCL is not a single disease but rather a group of related conditions. Healthcare experts have identified more than a dozen different types of DLBCL^[2][8]. Each type has unique characteristics that help doctors understand how the cancer will likely behave and respond to treatment.

The World Health Organization classifies these subtypes based on several factors. The most important is the genetic changes found in the lymphoma cells^[2]. Other factors include where in the body the lymphoma starts and whether it is associated with a specific virus^[2].

Some of the recognized subtypes include:

• DLBCL not otherwise specified (NOS): This is the most common category. When a case doesn’t fit into one of the more specific subtypes, it is classified as DLBCL NOS^[3][5].
• T-cell/histiocyte-rich B-cell lymphoma: Under the microscope, this form shows a few scattered large cancer B cells surrounded by many normal T cells and histiocytes, which are cells that come from bone marrow^[3][8].
• Primary DLBCL of the central nervous system (CNS): This subtype starts in the brain or the eye^[3][8].
• Primary cutaneous DLBCL, leg type: This type typically appears as red or bluish-red tumors on the skin, often on the legs, but it can occur anywhere on the body^[3][8].
• Primary mediastinal B-cell lymphoma: This subtype starts in the center of the chest, in an area called the mediastinum^[2][8].
• Epstein-Barr virus (EBV)-positive DLBCL: This form occurs in patients who test positive for the Epstein-Barr virus and usually affects people age 50 or older^[3][8].

Understanding which subtype you have is important because it can affect your treatment plan and outlook. Your doctor can explain how your specific type of DLBCL will impact your care^[2].

Signs and symptoms

The most common symptom that people notice with DLBCL is swollen lymph nodes in the neck, armpits, or groin^[2][5]. These usually appear as a lump that doesn’t go away and may seem to be getting larger. The lump is usually not painful, but it can be^[2].

About 30 percent of people with DLBCL experience what doctors call “B symptoms”^[2]. These include:

• High fevers above 103 degrees Fahrenheit (39.5 degrees Celsius) that last longer than two days or come and go^[2][7]
• Unexplained weight loss, involving losing more than 10 percent of your body weight over six months^[2][7]
• Heavy night sweats that are so intense they drench your sheets^[2][7]

Some people may also experience unexplained itching^[5].

Because DLBCL can develop outside the lymph nodes, in areas such as the stomach, bowel, or chest, the symptoms depend on where the cancer is growing^[5][7]. For example, DLBCL growing in your abdomen or bowel might cause pain, diarrhea, or bleeding^[5]. If it grows in your chest, you might experience breathlessness or a cough^[5].

Other possible symptoms include an enlarged liver or spleen, fatigue, shortness of breath, and loss of appetite^[7].

It’s important to note that having these symptoms doesn’t necessarily mean you have DLBCL. However, you should contact a healthcare provider if you notice any changes in your body that last for several weeks^[2][5].

What causes DLBCL?

DLBCL happens when B cells undergo changes or mutations in their genetic material^[2]. These are acquired genetic mutations, meaning you develop them during your lifetime rather than being born with them^[2].

The exact reasons why these mutations occur are not fully understood^[7]. Like other cancers, B cell lymphomas can result from genetic changes that affect genes controlling cell growth and genes that normally suppress tumors^[4]. However, the environment within the lymph nodes can also contribute to the development of lymphoma^[4].

Medical researchers have identified more than 70 different genetic mutations linked to DLBCL^[7]. Changes in a gene called BCL6 can be found in 20 to 40 percent of patients^[4].

Certain infectious agents can play a role in some cases. The Epstein-Barr virus can transport its genetic material into B cell nuclei, changing how B cells grow and develop^[4]. Similarly, some types of DLBCL are associated with the Kaposi’s sarcoma-associated herpesvirus, HIV, or infection with the bacteria Helicobacter pylori^[8].

In some cases, DLBCL may develop from the transformation of other types of slower-growing lymphomas, including follicular lymphoma, marginal zone lymphomas, small lymphocytic lymphoma, and Waldenstrom macroglobulinemia^[4][8]. When DLBCL develops in people with chronic lymphocytic leukemia, this transformation is called Richter’s transformation^[8].

Who is at higher risk?

DLBCL can occur in childhood, but it generally becomes more common with age. Most patients are over the age of 60 at diagnosis^[3]. The median age at first diagnosis is about 70 years^[8][11]. The condition is more common among men than women^[7].

Several factors can increase the risk of developing DLBCL:

• A family history of lymphoma^[7]
• Having HIV or another condition that causes a weakened immune system^[4][7]
• Taking immunosuppressive medications, such as those used after organ transplants^[4]
• Infection with Epstein-Barr virus^[7]
• A history of a low-grade B-cell lymphoma or chronic lymphocytic leukemia^[7]
• Previous treatment with chemotherapy or radiation^[7]

Chronic problems with the immune system, such as decreased ability of T cells and B cells to function properly, may contribute to the development of lymphoma in people with HIV^[4].

How is DLBCL diagnosed?

Diagnosing DLBCL often begins with a physical exam. Your doctor will check for swollen lymph nodes in your neck, underarms, and groin, and will check if your spleen or liver is enlarged^[10].

The main test used to diagnose lymphoma is a biopsy, which involves removing part or all of a swollen lymph node^[5][10]. A specialist examines the tissue sample under a microscope to look for cancer cells^[5]. The biopsy can confirm whether you have DLBCL and identify which specific subtype you have^[10].

You may also have blood tests. These can sometimes show whether lymphoma cells are present and can test for viruses including Epstein-Barr virus, HIV, hepatitis B, and hepatitis C^[10]. Blood tests also measure levels of an enzyme called lactate dehydrogenase (LDH), which is often higher in people with lymphoma^[10].

If your doctor confirms you have lymphoma, you may need additional tests to determine how far the cancer has spread. These might include:

• Imaging tests such as MRI, CT scans, and PET scans to create pictures of the inside of your body and show the location and extent of the lymphoma^[5][10]
• A bone marrow biopsy, which involves collecting cells from the soft matter inside bones where blood cells are made, to check if lymphoma cells are present^[5][10]
• A lumbar puncture, which involves collecting fluid from around your brain and spine to check for lymphoma cells^[5][10]

Treatment options

Because DLBCL grows quickly, it usually requires immediate treatment^[9]. The good news is that this type of lymphoma often responds well to treatment. About 75 percent of patients treated initially for DLBCL respond well to standard chemotherapy-based therapy, and many people are cured of the condition^[7].

The most widely used first-line treatment for DLBCL is a combination called R-CHOP^[9][14]. This regimen includes:

• Rituximab (Rituxan), a targeted therapy drug
• Cyclophosphamide (Cytoxan)
• Doxorubicin (Adriamycin)
• Vincristine (Oncovin)
• Prednisone

R-CHOP is usually given in 21-day cycles, meaning treatment occurs on the first day of each cycle and is followed by 20 days of rest and recovery^[9][14]. Most people receive an average of six cycles, so treatment is typically completed in about six months^[9][14]. However, the length and number of cycles can vary based on your individual disease and health status^[9].

A newer option that has been approved is polatuzumab vedotin (Polivy) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, called pola-R-CHP^[9][11][12]. In this regimen, polatuzumab vedotin replaces vincristine. This combination is now standard of care for patients with intermediate- to high-risk disease^[12].

Some patients receive a related regimen called R-EPOCH, which involves the same drugs administered as a continuous infusion over four days^[9]. This may be preferred in certain cases, such as in people with HIV-related DLBCL^[9].

In some cases, treatment may also involve radiation therapy^[9]. This is especially common for limited stage disease (Stage I or II), where three to four cycles of chemotherapy may be followed by radiation^[9].

For patients whose disease returns or doesn’t respond well to initial treatment, there are several newer treatment options:

• CAR T-cell therapy, a type of immunotherapy where your own T cells are collected and modified in a laboratory to better recognize and attack cancer cells^[1][12][15]
• Stem cell transplantation, where high-dose chemotherapy is followed by infusion of healthy stem cells to rebuild your blood-forming system^[1][15]
• Bispecific antibodies, which bring immune T cells close to cancer cells to destroy them^[12]
• Antibody drug conjugates, such as loncastuximab tesirine, which deliver chemotherapy directly to cancer cells^[12]
• Targeted therapies combined with other drugs, such as lenalidomide with tafasitamab^[12][15]

Your healthcare team will work with you to develop a treatment plan that is right for your specific situation^[16].

What to expect

Despite being an aggressive lymphoma, DLBCL is considered potentially curable^[3]. Between 50 and 60 percent of all patients are cured with rituximab-based chemotherapy in the first-line setting^[11].

In one important study, patients who received R-CHOP spent an average of 2.9 years without their cancer advancing or needing a change in therapy, compared with an average of 1.1 years for patients who received chemotherapy without rituximab^[14]. Adding rituximab to chemotherapy reduced the risk of death by 32 percent compared to chemotherapy alone^[14].

Doctors use a tool called the International Prognostic Index (IPI) to help predict how well a person with DLBCL is likely to respond to treatment^[16]. The IPI looks at factors such as age, blood test results, disease stage, overall health status, and whether the lymphoma is in areas outside the lymph nodes^[16].

For patients whose disease returns or is resistant to treatment, outcomes have improved significantly in recent years with new therapies like CAR T-cell therapy and bispecific antibodies. Roughly 30 to 40 percent of patients have the potential to be cured with CAR T-cell therapy when used as second-line treatment^[12].

Relapsed or refractory disease is typically observed within the first two years after diagnosis^[11]. Treatment can cause acute and long-term side effects, and treatment-related mortality ranges between 2 and 8 percent^[11].

It’s important to stay in close contact with your healthcare team and report any new symptoms promptly. With ongoing advances in treatment, there are more options than ever before for managing this disease^[11].