Diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). It is an aggressive (fast-growing), but treatable, lymphoma that starts in B cells.

There are many different subtypes of DLBCL. They are classified based on the type of cell the lymphoma started in and certain genetic changes (molecular features) found in the cells.

Some types of indolent (slow-growing) B-cell lymphomas can change into DLBCL. These types of NHL include follicular lymphoma, marginal zone lymphomas, small lymphocytic lymphoma and Waldenstrom macroglobulinemia.

Having HIV or a weakened immune system increases the risk of certain types of DLBCL, such as HIV-associated DLBCL and Epstein-Barr virus-associated DLBCL.

The International Prognostic Index (IPI) was developed to help determine the outcome for people with aggressive (fast-growing) types of NHL, like DLBCL. Doctors use the IPI to help determine if NHL is likely to respond well to treatment and if it is likely to come back (relapse) after treatment.

The IPI includes the following poor prognostic factors:

• 60 years of age or older
• high lactate dehydrogenase (LDH) level
• stage 3 or 4
• performance status of 2 or higher
• lymphoma is in more than one place outside of the lymph nodes (called extranodal sites)

The poor prognostic factors are used to assign DLBCL to one of the following risk groups:

• low risk (0 or 1 poor prognostic factor)
• low–intermediate risk (2 poor prognostic factors)
• high–intermediate risk (3 poor prognostic factors)
• high risk (4 or 5 poor prognostic factors)

The IPI helps you and your healthcare team make treatment decisions that are right for you. This index is also used in clinical trials testing new drugs to treat NHL.

The following are treatment options for DLBCL. Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan.

Chemotherapy uses drugs to destroy cancer cells. It is usually combined with a targeted therapy drug as the main treatment for DLBCL. The most common targeted therapy drug used is rituximab (Rituxan and biosimilars) .

The number of chemotherapy cycles that are given as treatment will depend on:

• the stage of DLBCL (limited, advanced, relapsed or refractory)
• if there are large areas of disease (called bulky disease)
• IPI prognostic factors
• your overall health

Find out more about chemotherapy for NHL.

R-CHOP is usually the first chemotherapy combination offered as treatment for DLBCL. R-CHOP is rituximab, cyclophosphamide (Procytox), doxorubicin, vincristine and prednisone. R-CHOP is given for up to 6 cycles.

After you finish the recommended chemotherapy cycles, you will have a PET scan to measure the response to treatment.

• If there is a complete response, you may not need further treatment, or you may be given one more cycle of R-CHOP or start radiation therapy.
• If there is a partial response, you may either have more cycles of chemotherapy (with or without radiation therapy) or radiation therapy alone.
• If there is no response to R-CHOP (DLBCL continues to grow, or progress), you will be treated with chemotherapy used for relapsed or refractory disease.

Sometimes the healthcare team may use other drug combinations instead of R-CHOP to treat DLBCL. These combinations include:

• ​R-CEOP – rituximab, cyclophosphamide, etoposide, vincristine and prednisone​
• Pola-R-CHOP – polatuzumab vedotin (Polivy), rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
• DA-EPOCH – dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin

If you have heart problems or are in poor health, you may be given the following instead of R-CHOP:

• DA-EPOCH-R
• R-mini-CHOP – R-CHOP chemotherapy with lower doses of doxorubicin

Dexrazoxane (Zinecard) is a drug that protects the heart from damage that some chemotherapy drugs can do. Dexrazoxane may also be added to these combinations.

If DLBCL responds to R-CHOP chemotherapy but then comes back after treatment has finished, it is called relapsed disease. Most relapses for DLBCL will happen 2 to 3 years after R-CHOP treatment has finished.

If DLBCL doesn't respond to R-CHOP, it is called refractory disease.

The chemotherapy combinations that may be used for relapsed or refractory DLBCL include:

• GDP – gemcitabine, dexamethasone and cisplatin
• R-GDP – rituximab, gemcitabine, dexamethasone and cisplatin
• R-ICE – rituximab, ifosfamide (Ifex), carboplatin and etoposide
• R-DHAP – rituximab, dexamethasone, cytarabine (Cytosar) and cisplatin
• R-GemOX – rituximab, gemcitabine and oxaliplatin
• Pola-BR – polatuzumab vedotin, bendamustine (Treanda, Benvyon, Esamuze) and rituximab

Sometimes your healthcare team may offer single drugs to treat relapsed or refractory DLBCL, including:

• cyclophosphamide
• cytarabine
• gemcitabine

A stem cell transplant replaces stem cells when stem cells, the bone marrow or both are damaged. A stem cell transplant is very risky and complex, and it must be done in a special transplant centre or hospital.

You may be offered an autologous stem cell transplant for relapsed or refractory DLBCL. This type of stem cell transplant uses your own stem cells rather than a donor's.

Your healthcare team may suggest stem cell transplant as a treatment option if:

• you are generally healthy
• DLBCL responds to chemotherapy (called chemosensitive)
• DLBCL has not spread to the brain and spinal cord (called the central nervous system, or CNS)
• your organs are working normally

Find out more about stem cell transplant for NHL.

Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them. 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. Targeted therapy may also be called molecular targeted therapy.

Targeted therapy may be used alone or in combination with chemotherapy or immunotherapy to treat DLBCL. The most common targeted therapy drug used is rituximab.

Other targeted therapy drugs that may be used to treat DLBCL that comes back after treatment (relapses) or doesn't respond to treatment (called refractory disease) include:

• polatuzumab vedotin (Polivy)
• tafasitamab (Minjuvi) in combination with lenalidomide (Revlimid)

These targeted therapy drugs may not be covered by all provincial or territorial health plans.

Find out more about targeted therapy for NHL.

Immunotherapy helps to strengthen or restore the immune system's ability to fight cancer. It is sometimes used to treat relapsed or refractory DLBCL. The following immunotherapy drugs may not be covered by all provincial or territorial health plans.

Your healthcare team may offer the immunotherapy called CAR T-cell therapy as a treatment option if:

• you have had 2 or more other types of chemotherapy
• you are generally healthy and your organs are working well
• you haven't received T-cell immunotherapy before
• DLBCL hasn't spread to the central nervous system (CNS)

The following drugs may be used in CAR T-cell therapy:

• tisagenlecleucel (Kymriah)
• axicabtagene ciloleucel (Yescarta)
• lisocabtagene maraleucel (Breyanzi)

Bispecific antibodies are a new type of immunotherapy. The following bispecific antibodies may be offered:

• epcoritamab (Epkinly)
• glofitamab (Columvi)

Find out more about immunotherapy for NHL.

Radiation therapy uses high-energy rays or particles to destroy cancer cells. It 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 lymphoma cells from spreading to it.

Sometimes radiation therapy is given after chemotherapy for more advanced stages of DLBCL or for relapsed or refractory DLBCL. It is used if there is still disease in a small area of the body or if there are tumours or areas of lymphoma that are 10 cm or bigger (called bulky disease).

Find out more about radiation therapy for NHL.

Talk to your doctor about clinical trials open to people with NHL in Canada. Clinical trials look at new ways to prevent, find and treat cancer. Find out more about clinical trials.