Non-Hodgkin's Lymphoma Treatment Option Overview

There are different types of treatment for patients with non-Hodgkin lymphoma.

Different types of treatment are available for patients with non-Hodgkin lymphoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

For pregnant women with non-Hodgkin lymphoma, treatment is carefully chosen to protect the fetus. Treatment decisions are based on the mother’s wishes, the stage of the non-Hodgkin lymphoma, and the trimester of the pregnancy. The treatment plan may change as the signs and symptoms, cancer, and pregnancy change. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.

Patients with non-Hodgkin lymphoma should have their treatment planned by a team of health care providers who are experts in treating lymphomas.

Treatment will be overseen by a medical oncologist, a doctor who specializes in treating cancer, or a hematologist, a doctor who specializes in treating blood cancers. The medical oncologist may refer you to other health care providers who have experience and are experts in treating non-Hodgkin lymphoma and who specialize in certain areas of medicine. These may include the following specialists:

• Neurosurgeon.
• Neurologist.
• Radiation oncologist.
• Endocrinologist.
• Rehabilitation specialist.
• Fertility specialist.
• Other oncology specialists.

Treatment for non-Hodgkin lymphoma may cause side effects.

To learn more about side effects that begin during treatment for cancer, visit Side Effects.

Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects. Treatment with chemotherapy, radiation therapy, or stem cell transplant for non-Hodgkin lymphoma may increase the risk of late effects.

Late effects of cancer treatment may include the following:

• Heart problems.
• Infertility (inability to have children).
• Loss of bone density.
• Neuropathy (nerve damage that causes numbness or trouble walking).
• A second cancer, such as:
  • Lung cancer.
  • Brain cancer.
  • Kidney cancer.
  • Bladder cancer.
  • Melanoma.
  • Hodgkin lymphoma.
  • Myelodysplastic syndrome.
  • Acute myeloid leukemia.

Some late effects may be treated or controlled. It is important to talk with your doctor about the effects cancer treatment can have on you. Regular follow-up to check for late effects is important.

The following types of treatment are used:

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing.

External radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer. Sometimes total-body irradiation is given before a stem cell transplant.

Proton beam radiation therapy is a type of high-energy, external radiation therapy that uses streams of protons (tiny particles with a positive charge) to kill tumor cells. This type of treatment can lower the amount of radiation damage to healthy tissue near a tumor such as the heart or breast.

External radiation therapy is used to treat non-Hodgkin lymphoma, and may also be used as palliative therapy to relieve symptoms and improve quality of life.

For a pregnant woman with non-Hodgkin lymphoma, radiation therapy should be given after delivery, if possible, to avoid any risk to the fetus. If treatment is needed right away, the woman may decide to continue the pregnancy and receive radiation therapy. A lead shield is used to cover the pregnant woman's abdomen to help protect the fetus from radiation as much as possible.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using two or more anticancer drugs. Steroid drugs may be added, to lessen inflammation and lower the body's immune response.

Systemic combination chemotherapy is used for the treatment of non-Hodgkin lymphoma.

Intrathecal chemotherapy may also be used in the treatment of lymphoma that first forms in the testicles or sinuses (hollow areas) around the nose, diffuse large B-cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, and some aggressive T-cell lymphomas. It is given to lessen the chance that lymphoma cells will spread to the brain and spinal cord. This is called CNS prophylaxis.

When a pregnant woman is treated with chemotherapy for non-Hodgkin lymphoma, the fetus cannot be protected from being exposed to chemotherapy. Some chemotherapy regimens may cause birth defects if given in the first trimester.

For more information, see Drugs Approved for Non-Hodgkin Lymphoma.

Immunotherapy

Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer.

• Immunomodulators: Lenalidomide is an immunomodulator used to treat non-Hodgkin lymphoma.
• CAR T-cell therapy: The patient's T cells (a type of immune system cell) are changed so they will attack certain proteins on the surface of cancer cells. T cells are taken from the patient and special receptors are added to their surface in the laboratory. The changed cells are called chimeric antigen receptor (CAR) T cells. The CAR T cells are grown in the laboratory and given to the patient by infusion. The CAR T cells multiply in the patient's blood and attack cancer cells. CAR T-cell therapy (such as axicabtagene ciloleucel or tisagenlecleucel) is used to treat large B-cell lymphoma that has not responded to treatment. CAR T-cell therapy is being studied to treat mantle cell lymphoma that has relapsed or not responded to treatment.

For more information, see Drugs Approved for Non-Hodgkin Lymphoma.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Monoclonal antibody therapy, proteasome inhibitor therapy, and kinase inhibitor therapy are types of targeted therapy used to treat non-Hodgkin lymphoma.

• Monoclonal antibody therapy: Monoclonal antibodies are immune system proteins made in the laboratory to treat many diseases, including cancer. As a cancer treatment, these antibodies can attach to a specific target on cancer cells or other cells that may help cancer cells grow. The antibodies are able to then kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

  Types of monoclonal antibodies include:

  • Rituximab, used to treat many types of non-Hodgkin lymphoma.
  • Obinutuzumab, used to treat follicular lymphoma.
  • Mogamulizumab, used to treat certain types of relapsed or refractory T-cell lymphoma.
  • Tafasitamab combined with lenalidomide to treat relapsed or refractory diffuse large B-cell lymphoma.
  • Pembrolizumab to treat primary mediastinal large B-cell lymphoma.
  • Polatuzumab vedotin, combined with bendamustine and rituximab to treat relapsed or refractory diffuse large B-cell lymphoma.
  • Brentuximab vedotin, which contains a monoclonal antibody that binds to a protein called CD30 that is found on some lymphoma cells. It also contains an anticancer drug that may help kill cancer cells.
  • Yttrium Y 90-ibritumomab tiuxetan, an example of a radiolabeled monoclonal antibody.
  • Mosunetuzumab, which is a bispecific monoclonal antibody that helps the body's immune system recognize and kill cancer cells. It is used to treat relapsed or refractory follicular lymphoma.
• Proteasome inhibitor therapy: This treatment blocks the action of proteasomes in cancer cells. Proteasomes remove proteins no longer needed by the cell. When the proteasomes are blocked, the proteins build up in the cell and may cause the cancer cell to die. Bortezomib or ixazomib is used to decrease how much immunoglobulin M is in the blood after cancer treatment for lymphoplasmacytic lymphoma (Waldenström macroglobulinemia). It is also being studied to treat relapsed mantle cell lymphoma.
• Kinase inhibitor therapy: This treatment blocks certain proteins, which may help keep lymphoma cells from growing and may kill them. Kinase inhibitor therapies include:
  • Ibrutinib, acalabrutinib, and zanubrutinib, which are types of Bruton tyrosine kinase inhibitor therapy. They are used to treat mantle cell lymphoma. Ibrutinib and acalabrutinib are also used to treat lymphoplasmacytic lymphoma, and zanubrutinib is being studied to treat it.
• Histone methyltransferase inhibitor therapy: Tazemetostat is used to treat follicular lymphoma that has come back or has not gotten better with other treatment. It is used in adults whose cancer has a certain mutation (change) in the EZH2 gene that has already been treated with at least two other anticancer therapies.
• B-cell lymphoma-2 (BCL-2) inhibitor therapy: Venetoclax may be used to treat mantle cell lymphoma. It blocks the action of a protein called BCL-2 and may help kill cancer cells.

For more information, see Drugs Approved for Non-Hodgkin Lymphoma.

Plasmapheresis

If the blood becomes thick with extra antibody proteins and affects circulation, plasmapheresis is done to remove extra plasma and antibody proteins from the blood. In this procedure, blood is removed from the patient and sent through a machine that separates the plasma (the liquid part of the blood) from the blood cells. The patient's plasma contains the unneeded antibodies and is not returned to the patient. The normal blood cells are returned to the bloodstream along with donated plasma or a plasma replacement. Plasmapheresis does not keep new antibodies from forming.

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change.

Antibiotic therapy

Antibiotic therapy is a treatment that uses drugs to treat infections and cancer caused by bacteria and other microorganisms.

Surgery

Surgery may be used to remove the lymphoma in certain patients with indolent or aggressive non-Hodgkin lymphoma.

The type of surgery used depends on where the lymphoma formed in the body:

• Local excision for certain patients with mucosa-associated lymphoid tissue (MALT) lymphoma, PTLD, and small bowel T-cell lymphoma.
• Splenectomy for patients with marginal zone lymphoma of the spleen.

Patients who have a heart, lung, liver, kidney, or pancreas transplant usually need to take drugs to suppress their immune system for the rest of their lives. Long-term immunosuppression after an organ transplant can cause a certain type of non-Hodgkin lymphoma called posttransplant lymphoproliferative disorder (PLTD).

Small bowel surgery is often needed to diagnose celiac disease in adults who develop a type of T-cell lymphoma.

Stem cell transplant

Stem cell transplant is a method of giving high doses of chemotherapy and/or total-body irradiation and then replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient (autologous transplant) or a donor (allogeneic transplant) and are frozen and stored. After the chemotherapy and/or radiation therapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body’s blood cells.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI website.

Vaccine therapy

Vaccine therapy is a cancer treatment that uses a substance or group of substances to stimulate the immune system to find the tumor and kill it.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Follow-up tests may be needed.

As you go through treatment, you will have follow-up tests or check-ups. Some tests that were done to diagnose or stage the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back).