Watchful Waiting/Active Surveillance

Some forms of non-Hodgkin lymphoma are slow growing and don't require initial treatment. The doctor closely monitors the cancer with regular screening and diagnostic tests, and would administer standard treatments if the lymphoma shows signs of significant growth or the patient begins to have symptoms.

Chemotherapy

Chemotherapy in combination with immunotherapy is the main treatment for non-Hodgkin lymphoma. Chemotherapy refers to the use of drugs to target rapidly growing cells in order to destroy cancer cells. Chemotherapy drugs can be administered through a vein (intravenously) or by mouth (orally). Doctors generally provide a combination of different chemotherapy drugs to treat non-Hodgkin lymphoma. For some patients who do not respond well to these regimens, doctors may recommend high-dose chemotherapy with stem cell transplant or chimeric antigen receptor T-cell (CAR-T) therapy.

Radiation Therapy

Radiation therapy uses waves of high-energy rays produced in a precise way from a machine to destroy lymphoma cells that are found in nodes or tumor masses. The doctor may recommend radiation after completion of chemotherapy to kill any lymphoma that may be left over after the chemotherapy. Doctors also sometimes give radiation alone to treat some cases of early-stage non-Hodgkin lymphoma. A doctor who gives these kinds of treatments is called a radiation therapist, or radiation oncologist. These doctors commonly use a radiation technique called involved-field radiotherapy to treat lymphomas. This technique allows them to target only the area of the body where the lymphoma is located.

Proton beam radiation therapy

Proton therapy is an advanced type of radiation therapy that uses “protons” rather than X-ray “photons” to deliver radiation to the tumor. In conventional radiotherapy, the photon beams can deposit radiation and damage healthy cells as they pass through the body. Proton therapy deposits most of the radiation directly at the tumor site, resulting in less damage to healthy tissue and fewer side-effects.

• Please see Understanding Proton Therapy to learn more.

Monoclonal Antibody Therapy

This treatment uses drugs called monoclonal antibodies, which mimic the immune system to target and destroy cancer cells. These antibodies, a form of immunotherapy, are designed to bind to specific proteins (antigens) on lymphoma cells, either killing the cells directly or helping the immune system recognize and attack them.

For slower-growing lymphomas, monoclonal antibodies can be used alone or combined with other oral targeted therapies. In aggressive B-cell lymphomas, they are typically combined with chemotherapy or other targeted treatments as part of standard care.

Rituximab, the most commonly used monoclonal antibody in B-cell lymphomas, targets the CD20 protein and is used both at diagnosis and in relapsed or refractory disease. Obinutuzumab is another CD20-targeting antibody with similar uses. Other antibodies target different antigens—tafasitamab targets CD19 and is approved for relapsed diffuse large B-cell lymphoma. Antibodies against PD-1 (programmed death-1) have shown effectiveness in certain rare B-cell lymphoma subtypes. Additionally, mogamulizumab, which targets CCR4, is used to treat cutaneous T-cell lymphoma, a rare form of the disease.

Antibody Drug Conjugates

Antibody-drug conjugates (ADCs) are special treatments that combine an antibody with a small amount of chemotherapy. The antibody helps guide the chemotherapy directly to the cancer cells, which may reduce damage to healthy cells.

One example is brentuximab vedotin, which targets a protein called CD30. It’s approved for use with chemotherapy as a first treatment for T-cell lymphomas, and it's also used when the disease comes back or doesn’t respond to other treatments. Brentuximab is also approved as part of a combination treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Another ADC, polatuzumab vedotin, targets the CD79b protein and is approved for certain patients with diffuse Large B-Cell Lymphoma (DLBCL), both as a first treatment and for those whose disease has returned or stopped responding to other therapies.

Loncastuximab tesirine is another ADC that targets CD19 and is approved for relapsed or refractory DLBCL.

Researchers are continuing to study other ADCs that target different proteins, and more options may become available through clinical trials.

Radioimmunotherapy

Radioimmunotherapy is treatment with monoclonal antibodies that have radioactive molecules attached to them. The monoclonal antibodies carry the radiation to the cancer cells. Radioimmunotherapy is often more effective than non-radioactive antibodies, and is approved in the United States for therapy of patients with slow-growing lymphomas.

Stem Cell Transplantation

This procedure allows patients to receive large doses of chemotherapy. High doses destroy lymphoma cells in the patient's body, but also cause significant damage to normal cells in the bone marrow. After chemotherapy, the patient receives blood-forming stem cells that help the body form new, healthy blood cells in the bone marrow. In an autologous stem-cell transplant, the stem cells are collected from the patient prior to the administration of high dose therapy. In an allogeneic transplant, the stem cells are collected from a healthy donor.

Protein and Small Molecule Inhibitors Targeted therapies

Targeted therapies are a newer type of cancer treatment that work by blocking specific proteins cancer cells need to grow and survive. Some of these therapies also stop the cancer from creating new blood vessels, which it needs to grow. These treatments are especially promising for patients with lymphoma and are being actively studied in clinical trials.

Many of these drugs are already approved for use in relapsed or refractory lymphoma (lymphoma that has come back or didn’t respond to treatment), and some are now being tested as part of initial treatment in combination with other therapies.

Immunomodulators

Immunomodulators stimulate the patient's immune system to help it fight off lymphoma cells, but also have other ways to control the growth of cancer cells. These new medicines also appear very promising for therapy of lymphomas, including the oral immunomodulator lenalidomide which is approved alone or in combination with immunotherapy in various B cell lymphomas

CAR-T Immunotherapy

One exciting type of immunotherapy approved for some B-cell lymphomas, especially when the disease comes back or doesn’t respond to treatment, is called CAR T-cell therapy.

This treatment uses a person’s own immune cells, specifically T-cells, which are collected from their blood. In the lab, these T-cells are genetically modified to produce special proteins on their surface called CARs (chimeric antigen receptors). These CARs help the T-cells recognize and attack cancer cells more effectively.

Once the T-cells are modified, they are returned to the patient through an infusion. After entering the body, the CAR T-cells multiply and go to work—finding and destroying cancer cells with the help of their new receptors.

Currently approved CAR T-cell treatments target a protein called CD19, which is found on B-cell cancer cells. Researchers are now studying new versions that target other proteins, or even multiple proteins at once, to make the treatment work even better.