Diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). When looked at under a microscope, the lymphoma cells look very large compared to normal lymphocytes. The lymphoma cells are also scattered throughout the lymph nodes or tissue.

DLBCL can occur at any age, but most people are diagnosed when they are in their mid-60s. It is slightly more common in men.

Most of the time, DLBCL starts in the lymph nodes but it can also start in organs or tissues outside of the lymph nodes (called primary extranodal disease). The most common places where DLBCL develops outside of the lymph nodes are the:

  • bones
  • brain or spinal cord (called the central nervous system, or CNS)
  • gastrointestinal (GI) tract
  • sinuses
  • testicles
  • thyroid
  • skin

In 30%–40% of cases, DLBCL is localized (stage 1 or 2) when it is diagnosed. The rest are widespread at the time of diagnosis. This means that DLBCL has spread to lymph nodes above and below the diaphragm or to different parts of the body, such as the spleen, liver or bone marrow.

Rare subtypes of DLBCL include:

DLBCL is a fast-growing (aggressive) type of NHL. Some types of slow-growing (indolent) B--cell lymphomas can change into DLBCL. These types include:

  • follicular lymphoma
  • MALT lymphoma
  • splenic marginal zone lymphoma
  • small lymphocytic lymphoma
  • lymphoplasmacytic lymphoma


With DLBCL, the lymph nodes grow larger than normal so that they can be felt. It can also cause B symptoms, which are unexplained fever, drenching night sweats and unexplained weight loss.


DLBCL is very sensitive to chemotherapy, so it is used as the main treatment. Even though DLBCL is a fast-growing type of NHL, chemotherapy is effective for many people. DLBCL may come back (recurs), after the first treatments are given.


Chemotherapy is used to treat all stages of DLBCL. The combination chemotherapy most often used first to treat DLBCL is CHOP:

  • cyclophosphamide (Cytoxan, Procytox)
  • doxorubicin (Adriamycin)
  • vincristine (Oncovin)
  • prednisone

Chemotherapy is usually given with a targeted therapy drug. R-CHOP is the same combination of chemotherapy with rituximab (Rituxan).

If DLBCL comes back after or doesn’t respond to treatment, the following chemotherapy drugs will be used:

  • R-GDP – gemcitabine (Gemzar), dexamethasone (Decadron, Dexasone), cisplatin (Platinol AQ) and rituximab
  • R-DHAP – dexamethasone, cytarabine (Cytosar, Ara-C), cisplatin and rituximab
  • cytarabine
  • bendamustine (Treanda)
  • PEPC – prednisone, etoposide (Vepesid, VP-16), cyclophosphamide and procarbazine (Natulan)
  • R-ICE – ifosfamide (Ifex), carboplatin (Paraplatin, Paraplatin AQ), etoposide and rituximab

Targeted therapy

Targeted therapy uses drugs to target specific molecules (such as proteins) on the surface of cancer cells. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells while limiting harm to normal cells.

Rituximab is a targeted therapy drug commonly used alone or in combination with chemotherapy to treat DLBCL.

Polatuzumab vedotin (Polivy) is a targeted therapy drug that may also be used to treat DLBCL. It is combined with bendamustine (Treanda) and rituximab for DLBCL that comes back after treatment or did not respond to treatment.

Tafasitamab (Minjuvi) may be used to treat relapsed or refractory DLBCL. It is given in combination with the immunotherapy drug lenalidomide (Revlimid).

Radiation therapy

External beam radiation therapy may be given after chemotherapy to treat stage 1 (and sometimes stage 2) DLBCL. When DLBCL develops in a testicle, radiation therapy may be given to the other testicle to prevent the spread of lymphoma cells.

Sometimes radiation therapy is given after chemotherapy for more advanced stages of DLBCL. It is used if there is still disease in a small area or if there are other areas with tumours that are 10 cm or more across (called bulky disease).

Central nervous system prophylaxis

The central nervous system (CNS) is the brain and spinal cord. DLBCL that starts in the sinuses or testicles can spread to the CNS. CNS prophylaxis is used to try to prevent lymphoma cells from spreading to the brain and spinal cord.

CNS prophylaxis may be given as intrathecal chemotherapy. This means that the chemotherapy drug is injected directly into the cerebrospinal fluid (CSF). The drug used in intrathecal chemotherapy is methotrexate.

CNS prophylaxis can also be given with a needle into a vein (intravenously). The drug used for intravenous chemotherapy is high-dose methotrexate.

Stem cell transplant

People with DLBCL that doesn’t go away with treatment or that comes back (recurs) after treatment may be offered alternative treatments. These treatments may include other types of chemotherapy or a stem cell transplant. A stem cell transplant may be an option if the DLBCL responded to chemotherapy in the past.


People with DLBCL that doesn’t go away with treatment or that comes back after other treatments may be offered immunotherapy called CAR T-cell therapy.

CAR T-cell therapy takes millions of T cells from a person with cancer. In the lab, they are changed so they have chimeric antigen receptors (CARs) on their surface. These receptors recognize a specific antigen (protein) found on the type of cancer being treated. The T cells are then given back to the person where they multiply, attack and destroy the cancer cells.

CAR T-cell therapy with either tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) is approved to treat people with DLBCL that has relapsed (come back after treatment) or is refractory (not responded to treatment) after at least 2 other treatments. This includes DLBCL not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.

Expert review and references