Diffuse Large B Cell Lymphoma (DLBCL)

Table of Contents

Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma (NHL). NHL describes a group of blood cancers that develop in the white blood cells (leukocytes). DLBCL accounts for around one-third of NHL cases, mostly in older adults. The average age at diagnosis is mid-60s to 70 years old. In rare cases, DLBCL occurs in children and younger adults.

DLBCL usually begins as a mass or tumor in a lymph node. It can start in many different places in the body. It is considered an aggressive form of lymphoma meaning that it grows fast. Even so, treatment is often effective, and some patients are cured.

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Types of DLBCL

Non-Hodgkin lymphoma (NHL) includes many different types. They are broadly grouped as B-cell lymphomas or T-cell lymphomas. DLBCL is the most common B-cell lymphoma. Follicular lymphoma is a slow-growing B-cell lymphoma. It sometimes turns into DLBCL over time.

Within DLBCL, there are many rare subtypes, including:

  • Primary mediastinal (thymic) B-cell lymphoma begins as a mass in the chest and can affect breathing. It occurs mostly in people in their 30s who were born female. Like primary DLBCL, it is fast-growing but often treatable.
  • Primary DLBCL of the central nervous system begins in or near the brain, spinal cord, or eyes. It occurs more often in middle-aged people who were born male. It is also found in people with weakened immune systems including those with AIDS.
  • Cutaneous leg type DLBCL first appears as lesions on the legs. It is more common among older people who were born female.

Doctors also sometimes use the germinal center (GC) to describe DLBCL. It can be GC or NGC (non-germinal center). The germinal center is an area where many B cells are found and grow. Cancers that have germinal centers respond differently to treatment than those that do not.

Risk Factors

Risk factors are things that can increase the chance of developing a disease. Certain cancer risk factors, such as smoking, can be changed.

Other cancer risk factors, such as a person’s age or family history, cannot be changed. Other cancer risk factors, like a person’s age or family history, cannot be changed. Having one or even many risk factors does not mean that a person will get the disease.

The risk factors for DLBCL are similar to those for other NHLs:

  • Age – Although DLBCL can develop at any age, most people are diagnosed at age 60 or older.
  • Sex at Birth – DLBCL occurs more often in people who are born male. Some subtypes are more common in people who are born female.
  • Geography – DLBCL is more common in developed countries.
  • Race and Ethnicity – In the U.S., DLBCL is most common among white people. It is less common among African Americans and Asian Americans/Pacific Islanders.
  • Autoimmune Disease – People with certain autoimmune diseases like lupus or rheumatoid arthritis may have a higher risk. This is due to the drugs they take to suppress the immune system.
  • Weakened Immune System – The risk of NHL is higher among people with weakened immune systems. This includes people with human immunodeficiency virus (HIV).
  • Organ Transplant Recipients – The drugs taken by people who receive organ transplants may increase risk. This is because they suppress the immune system to ensure that the body does not reject the new organ.
  • Radiation Exposure – Exposure to atomic bombs and nuclear reactor accidents can increase the risk of developing NHL. People treated with radiation therapy for certain cancers also may have a slightly higher risk of developing NHL.
  • Chemical Exposure – People who are exposed to certain weed killers and pesticides may have a higher risk of DLBCL. Exposure to benzene may also increase risk.
  • Past Cancer Treatment – Past treatment with chemotherapy or radiation therapy may increase the risk of DLBCL.
  • Viral Infection – People who have had Epstein-Barr virus may have a higher risk of DLBCL.
  • Body Weight – The relationship between DLBCL and weight is still being studied. Early studies have found that obesity may increase risk of developing DLBCL. Yet, people who are overweight may be less likely to die of DLBCL.

Signs & Symptoms

Many of the signs and symptoms of DLBCL are similar to those other lymphomas. Common signs and symptoms may include:

  • Abdominal Swelling - A tumor or large collection of fluid may cause the abdomen to become swollen and tender. Swelling may block the passage of feces. This causes abdominal pain, nausea, or vomiting.
  • Central Nervous System Changes - DLBCL may cause severe headaches, changes in personality, difficulty moving parts of the body, or seizures.
  • Coughing and Breathing Issues - Certain types of lymphoma can develop into large tumors in the chest. If the tumor presses on the windpipe it causes trouble breathing.
  • Fatigue and Loss of Appetite - Sometimes the only signs of the disease are constant tiredness and not feeling hungry.
  • Fever - A high temperature may occur over several days or weeks.
  • Lumps - Painless lumps or swollen lymph nodes may develop in the neck, underarm or groin area.
  • Night Sweats - You may wake up drenched in sweat.
  • Weight Loss - You may lose weight without dieting or attempting weight loss. 

Diagnosis

Lymphoma can be hard to diagnose. A complete diagnosis often takes more than one doctor’s visit. It may involve a physical exam, blood tests, scans, and a biopsy. These tests will confirm the exact type and stage of disease. Your health care team will first determine if you have lymphoma, then if it is DLBCL.

A biopsy will be needed to confirm that you have DLBCL. In a biopsy, tissue is removed and sent to a lab for study. Doctors diagnose NHL based on: (1) how the cells look under a microscope, (2) any genetic changes in the lymphoma cells, and (3) the presence of certain markers on the surface of the cells. In DLBCL, the cells are large and spread apart. Around 5% of DLBCLs are “double hit.” This means that two genes (MYC, BCL2, or BCL6) in the cell have switched places. Triple hit, which is even rarer, involves all three genes.

Two kinds of biopsies are used to diagnose NHL and, as such, DLBCL:

  • Lymph Node Biopsy - The doctor will remove a piece of the lymph node and examine it under a microscope. This is the only way to know for sure if the swelling is caused by cancer. The doctor will get as large of a sample as possible to determine the specific type of NHL. This sometimes requires surgery. Surgery is also used if the lymph node is in a location that is more difficult to reach.
  • Bone Marrow Biopsy - The doctor will insert a needle into your hipbone to check to see if lymphoma cells are present in your bone marrow. 

If a biopsy confirms a DLBCL diagnosis, your doctor may recommend more tests to find out how far the disease has spread. These other tests could include a chest x-ray, CT scan, MRI, PET scan, or blood tests.

Staging

After confirming a DLBCL diagnosis, the doctor needs to know the stage, or extent, of the disease to plan the best treatment. Staging is used to find out whether the cancer has spread, and if so, to which parts of the body.

Doctors use the Lugano Staging System to describe NHL. It is based on a similar system called Ann Arbor. Stages are assigned Roman numerals I-IV (1-4). A higher number means the disease is more advanced. Letters are added to the stages to provide more information. Although most lymphomas are stage III or IV when diagnosed, they are often treatable and possibly curable.

Stage I

Cancer is found in only one lymph node area or organ in the lymph system, such as the thymus gland (I).  The letters IE (extranodal) are used when the cancer is in one area of an organ outside the lymph system (e.g., lung, liver, bone, etc.).

Stage II

Cancer is found in two or more lymph node areas on the same side of the diaphragm. The diaphragm is the muscle below the lungs. It separates the chest and abdomen. Doctors use it as a dividing line when they stage lymphoma. When the cancer has spread to a nearby organ, it is considered IIE.

Stage III

Cancer is found in lymph nodes on both sides of the diaphragm (above and below it) (III). It has also spread to nearby organs (IIIE), the spleen (IIIS), or both (IIIES). 

​​​​​Stage IV 

The cancer has spread to one or more organs outside of the lymph system. For example it may have spread to the liver, bone marrow, or lung.

These letters may be added to the stage number to provide more information:

​​​​​Letter "A"

Added if the B symptoms (listed below) are not present.

​​​​​Letter "B"

Added if these symptoms are present: a loss of more than 10% of body weight over six months (without dieting or a lot of exercise), a fever of at least 100.4°F (38 degrees Celsius) without a known cause, or drenching night sweats.

​​​​​Letter "E"

Added if DLBCL has affected an organ outside of the lymph system.

​​​​​Letter "S"

Added when DLBCL affects the spleen.

​​​​​Letter "X" or “bulky”

Used when tumors are at least 10 centimeters (around 4 inches), which may require more intense treatment.

Doctors also use the revised International Prognostic Index (R-IPI) score to describe DLBCL. This score is based on five factors. Taken together, these factors help doctors estimate a patient’s prognosis—how they will respond to treatment. Points are assigned for each item. The total number of points helps predict the risk of disease relapse.

The index includes five factors:

  1. The person’s age – whether they are 60 and older
  2. The stage of lymphoma – is it stage III or IV
  3. Whether cancer is in organs outside the lymph system
  4. The patient’s ability to perform physical activities and normal activities of daily living
  5. The level of the enzyme lactate dehydrogenase (LDH) in the person’s blood
Duration: 54 min

New Options When Diffuse Large B Cell Lymphoma (DLBCL) Doesn't Respond to Treatment

  CSC's CEO, Linda Bohannon, RN, BSN, MSM, interviews Kami Maddocks, MD, about the newest treatments for relapsed/refractory Diffuse Large B Cell Lymphoma (DLBCL). They will discuss the latest treatment options, current clinical trials, and…

Treatments & Side Effects

DLBCL is an aggressive or fast-growing cancer so it usually needs to be treated right away. Treatment is often effective, and some patients are considered cured.

Your doctor will recommend treatment options based on the stage of the DLBCL, your overall health, and your treatment preferences. The most common treatment involves chemotherapy combined with immunotherapy.

Treatment Options

Chemotherapy

Chemotherapy uses drugs to destroy cancer cells. It is a systemic (whole body) treatment. This means it can destroy cancer cells almost anywhere in your body. It may be given by IV (through a vein), in pill form (by mouth), as an injection (a shot), applied directly on the skin into the area around the tumor, or placed directly into the tumor site. Most often, chemo is given in an outpatient clinic. You will have a regular schedule of treatments for a set period of time.

Chemotherapy is most effective against fast growing cells, like cancer. But some healthy, normal cells may also be damaged by this treatment. The side effects will vary depending on the drug(s) you take, the dose of your drugs, and how often you get treatments. Common side effects include mouth sores, fatigue, hair loss, nausea, “chemo brain,” and low blood cell or platelet counts.

A common chemotherapy combination for DLBCL is called CHOP. It includes four drugs given at once. They are cyclophosphamide (Cytoxan®), doxorubicin (hydroxydoxorubicin), vincristine (Oncovin®), and prednisone.

CHOP is often given with an immunotherapy drug called rituximab (Rituxan® and its biosimilars RiabniTM, RuxienceTM, & Truxima©). See our Immunotherapy section (below) for more information on rituximab. Doctors call this drug combination R-CHOP. It is an effective treatment for many DLBCLs.

Rituxan may be given in shot form with hyaluronidase (Rituxan Hycela). It is s a five- to seven-minute injection. This treatment is combined with chemotherapy.

New drugs are being tested in clinical trials. Talk with your doctor about your options.

Stem Cell Transplant

A stem cell transplant is an infusion of blood-forming cells (stem cells), not a surgery. The procedure has two parts. First, you will receive high doses of chemotherapy. This destroys blood cells. Next, stem cells are introduced into the bloodstream to replace blood cells. Bone marrow transplant is one kind of stem cell transplant. Sometimes patients serve as their own donors (autologous stem cell transplant). Other times, patient get stem cells from donors (allogeneic stem cell transplant).

Side effects are mainly due to the chemotherapy. They can include nausea, vomiting, diarrhea, mucositis (painful mouth sores), and fatigue. Doctors monitor patients closely to watch for serious side effects such as very low blood counts and hard-to-treat infections.

Learn More About Stem Cell Transplants

Immunotherapy

Immunotherapy uses the body’s natural defenses (the immune system) to find, attack, and kill cancer cells. Common side effects include fatigue, skin problems, or muscle or joint pain. Most side effects can be treated early and are easy to manage. Less often, side effects can be severe and even life-threatening.

One type of immunotherapy, monoclonal antibodies, may be used in combination with chemotherapy to treat DLBCL:

Rituximab (Rituxan®) and its biosimilars rituximab-arrx (RiabniTM), rituximab-pvvr (RuxienceTM), & rituximab-abbs (Truxima©) are used most often. Rituximab targets and binds to a marker (CD20) on the outside of the B-cells. This helps your immune system find and attack the cancer. Polatuzumab vedotin-piiq (Polivy) can also be used with a rituximab product, cyclophosphamide, docorubicin, and prednisone to treat DLBCL. Other drugs that target CD20 are obinutuzumab (Gazyva©) and ofatumumab (Arzerra©). They are sometimes used to treat DLBCL.

Another drug in this category that instead targets CD19 may be used when stem cell transplant is not possible. It is called tafasitamab-cxix (Monjuvi©).

When cancer returns (relapses) or does not respond to other treatments (is refractory), these immunotherapies may be used:

  • Immune checkpoint inhibitors – These drugs block pathways that block or slow immune response. The drug pembrolizumab (Keytruda©) may be used. It is also being tested for use before chemotherapy.
  • Cell therapies - CAR T-cell therapy [link to CAR T landing page] is sometimes used following a relapse of DLBCL after two prior lines of treatment. T cells are removed, altered, then returned to the body to fight cancer better. Three CAR T drugs approved for DLBCL are axicabtagene ciloleucel (Yescarta©), lisocabtagene maraleucel (Breyanzi©), and tisagenlecleucel (Kymriah©). They can only be given at approved centers with very close monitoring.

Other options may be available through clinical trials.

Learn More About Immunotherapy

Targeted Therapy

Targeted therapy aims to more precisely attack cancer cells. These drugs target changes in the genes or proteins of cancer cells that help them grow, divide, and spread. They treat the cancer cells with less harm to normal cells. There are different types of targeted therapy. You may get targeted therapy alone or in combination with other treatments, like chemotherapy or immunotherapy. Targeted therapy may be given as a pill (by mouth), as an IV (through a vein), or as an injection (shot). Ask if it is an option for you.

Common side effects include skin problems (rash, dry skin, itching), fatigue, or a flu-like reaction with fever, chills, and diarrhea.

Targeted drugs are used to treat DLBCL that does not respond to other treatments. They include:

  • selinexor (Xpovio©), a nuclear export inhibitor, kills cells at their core (nucleus)
  • ibrutinib (Imbruvica©), a kinase inhibitor
  • polutuzumab vedotin-piiq (PolivyTM), targets CD79b and delivers an anti-cancer drug directly to the cancer. It is an antibody-drug conjugate and is sometimes considered an immunotherapy too.
  • glofitamab-gxbm (ColumviTM), a bispecific CD20-directed CD3 T-cell engager.

Other targeted therapies that may be used to treat DLBCL include:

  • brentuximab vedotin (Adcetris©), an antibody-drug conjugate that targets CD30
  • lenalidomide (Revlimid©), an immunomodulator, may be given in combination with rituximab
  • epcoritamab-bysp (Epkinly™) is a bispecific CD20-directed CD3 T-cell engager.

Still other targeted therapies may be available through clinical trials.

Radiation Therapy

Radiation therapy is the use of high-energy rays to kill or damage cancer cells. It is given before, during, or after other treatments. The goal is to damage as many cancer cells as possible without harming healthy tissue. To lessen damage, doses are very precise, and treatment is often spaced out.

Common side effects include nausea, fatigue, and skin changes, such as redness, dryness, or itching at the site of treatment. Other side effects are specific to the part of the body being treated. Side effects can last after treatment is done.

Radiation therapy for DLBCL uses a focused beam of radiation from a machine outside of the body. External beam radiation is a painless procedure. It may be used after drug therapy or a stem cell transplant.

Coping With Side Effects

​​​​​It helps to learn more about the side effects of treatment before you begin so you will know what to expect. When you know more, you can work with your health care team to manage your quality of life during and after treatment.

There are many drugs available to treat the side effects of cancer treatment. Everyone reacts differently to treatment and experiences side effects differently. Talk to your health care team about your side effects so they can help you feel better. Your doctor may discuss options such as lowering the dose of your treatment if side effects persist and are not easy to manage. You may want to consult a palliative and supportive care specialist.

The following are common side effects:


You may also experience side effects of treatment well after your treatment has ended. It is important to talk to your doctor about long-term effects of treatment as part of your post-treatment plan.

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