Lymphoma - Non-Hodgkin: Treatment Options

Approved by the Cancer.Net Editorial Board, 02/2018

ON THIS PAGE: You will learn about the different treatments doctors use for people with this type of lymphoma. Use the menu to see other pages.

This section tells you the treatments that are the standard of care for this type of cancer. “Standard of care” means the best treatments known. When making treatment plan decisions, patients are encouraged to consider clinical trials as an option. A clinical trial is a research study that tests a new approach to treatment. Doctors want to learn whether the new treatment is safe, effective, and possibly better than the standard treatment. Clinical trials can test a new drug, a new combination of standard treatments, or new doses of standard drugs or other treatments. Your doctor can help you consider all your treatment options. To learn more about clinical trials, see the About Clinical Trials and Latest Research sections.

Treatment overview

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. Cancer care teams include a variety of other health care professionals, such as physician assistants, oncology nurses, social workers, pharmacists, counselors, dietitians, and others.

There are 4 main treatments for NHL:

  • Chemotherapy

  • Radiation therapy

  • Immunotherapy, such as monoclonal antibodies, immune checkpoint inhibitors, and CAR T cells

  • Targeted therapy with newer drugs that block certain functions within the lymphoma cell

Often, patients receive a combination of these treatments. Occasionally, the doctor and patient may consider surgery or stem cell transplantation.

Descriptions of these treatment options are listed below. Treatment options and recommendations depend on several factors, including:

  • The type and stage of NHL

  • Possible side effects

  • The patient’s preferences and overall health

Your care plan may also include treatment for symptoms and side effects, an important part of cancer care. Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Talk with your doctor about the goals of each treatment and what you can expect while receiving the treatment. Learn more about making treatment decisions.

Watchful waiting

Some people with indolent lymphoma may not need immediate treatment if they are otherwise healthy and the lymphoma is not causing any symptoms or problems with other organs. This is called watchful waiting, sometimes called watch-and-wait or active surveillance. During watchful waiting, doctors closely monitor patients using physical examinations, CT scans or other imaging tests, and laboratory tests on a regular basis. Treatment only begins if the person develops symptoms or tests indicate that the cancer is getting worse. For some people with indolent lymphoma, watchful waiting does not affect the chances of survival, but regular and careful follow-up care is recommended.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by ending the cancer cells’ ability to grow and divide. It is the main treatment for NHL. Chemotherapy is given by a medical oncologist, a doctor who specializes in treating cancer with medication, or a hematologist, a doctor who specializes in treating blood disorders. A medical oncologist or hematologist is most often the primary cancer specialist for people with lymphoma.

Systemic chemotherapy gets into the bloodstream to reach cancer cells throughout the body. Common ways to give chemotherapy include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally).

A chemotherapy regimen, or schedule, usually consists of a specific number of cycles given over a set period of time. A patient may receive 1 drug at a time or combinations of different drugs given at the same time. The chemotherapy regimen used depends on the stage and type of NHL. The most common chemotherapy combination for the initial treatment of aggressive NHL is called CHOP and contains 4 drugs:

  • Cyclophosphamide (Cytoxan, Neosar)

  • Doxorubicin (Adriamycin)

  • Prednisone (multiple brand names)

  • Vincristine (Oncovin, Vincasar)

For patients with B-cell lymphoma, adding the monoclonal antibody rituximab to CHOP works better than using CHOP alone (see  “Targeted therapy,” below). There are other common combinations of chemotherapy regimens, including:

  • BR (bendamustine and rituximab)

  • Fludarabine-based combinations (Fludara, Oforta)

  • R-CVP (cyclophosphamide, prednisone, rituximab, and vincristine)

The side effects of chemotherapy depend on the individual drug and the dose used. They can include fatigue, temporary lowering of blood counts, risk of infection, nausea and vomiting, hair loss, loss of appetite, rash, and diarrhea. These side effects can be managed during treatment and usually go away after treatment is finished.

Chemotherapy may also cause long-term side effects, also called late effects. People with lymphoma may also have concerns about if or how their treatment may affect their sexual health and fertility. Talk with the members of the health care team about these topics before treatment begins. Learn more about late effects of treatment.

Learn more about the basics of chemotherapy and preparing for treatment. The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions by using searchable drug databases.

Radiation therapy

Radiation therapy is the use of high-energy x-rays, electrons, or protons to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. Radiation treatment for NHL is usually external-beam radiation therapy, which is radiation given from a machine outside the body.

A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time.

Radiation therapy is usually given after or in addition to chemotherapy, depending on the NHL subtype. It is most often given to patients who have lymphoma that is localized, meaning it involves only 1 or 2 adjacent areas, or who have a lymph node that is particularly large, usually more than 7 to 10 centimeters across. It may also be given for the treatment of pain or in very low doses (just 2 treatments) to patients with advanced disease who have localized symptoms that can be relieved using radiation therapy.

General side effects from radiation therapy may include fatigue and nausea. Most side effects are related to the region of the body receiving radiation. These side effects may include mild skin reactions, dry mouth, temporary hair loss, or loose bowel movements. People who have had radiation therapy directed at the chest may experience lung inflammation called pneumonitis. People who had radiation therapy directed at the bones may experience low blood counts. Talk with your doctor about what you can expect regarding side effects and how they can be managed.

Most side effects go away soon after treatment is finished, but radiation therapy may also cause late effects, such as second cancers or damage to the heart and blood vessels if they were within the field of radiation. Sexual problems and infertility may occur after radiation therapy to the pelvis. Before treatment begins, talk with your doctor about possible sexual and fertility-related side effects of your treatment and the available options for preserving fertility for both men and women.

Learn more about the basics of radiation therapy.

Targeted therapy

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells while limiting damage to healthy cells.

Recent studies show that not all tumors have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your tumor. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, many research studies are taking place now to find out more about specific molecular targets and new treatments directed at them. Learn more about the basics of targeted treatments.

Monoclonal antibodies (updated 11/2018)

For NHL, monoclonal antibodies are the main form of targeted therapy used in the treatment plan. A monoclonal antibody recognizes and attaches to a specific protein and does not affect cells that don’t have that protein. A monoclonal antibody called rituximab is used to treat many different types of B-cell NHL. Rituximab works by targeting a molecule called CD20 that is located on the surface of all B cells and B-cell NHL. When the antibody attaches to this molecule, the patient’s immune system is activated to destroy some lymphoma cells or to make lymphoma cells more susceptible to being destroyed by chemotherapy.

Although the antibody may work well by itself, research shows that it worked better when added to chemotherapy for patients with most types of B-cell NHL. Rituximab is also given after remission for indolent lymphomas to increase the length of the remission. There are 3 other monoclonal antibodies against CD20 that are approved for use in lymphomas: obinutuzumab (Gazyva), ofatumumab (Arzerra), and rituximab-abbs (Truxima). Rituximab-abbs is called a biosimilar, which means that it functions in a way similar to rituximab (Rituxan). Learn more about biosimilars.

Brentuximab vedotin (Adcetris) is another type of monoclonal antibody, called an antibody-drug conjugate. Antibody-drug conjugates attach to targets on cancer cells and then release a small amount of chemotherapy or other toxins directly into the tumor cells. Brentuximab vedotin combined with chemotherapy is approved to treat adults with certain types of peripheral T-cell lymphoma, such as systemic anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, and peripheral T-cell lymphoma, not otherwise specified, as long as they express the CD30 protein. The drug was previously approved for people with Hodgkin lymphoma who did not benefit from or were unable to have a bone marrow transplant and for preventive treatment following a bone marrow transplant for higher-risk Hodgkin lymphoma. Research on the benefits of other newer monoclonal antibodies for lymphoma is ongoing.

Radiolabeled antibodies are monoclonal antibodies with radioactive particles attached. The particles are designed to focus the radiation directly to the lymphoma cells. In general, the radioactive antibodies are thought to be stronger than regular monoclonal antibodies but more damaging to the bone marrow. This type of therapy is also called radioimmunotherapy (RIT).

Talk with your doctor about possible side effects for a specific medication and how they can be managed.

Kinase inhibitors (updated 02/2019)

Kinase inhibitors are another type of targeted therapy used to treat NHL.

Copanlisib (Aliquopa) targets the phosphoinositide 3-kinase (PI3K) pathway. It is used to treat adults with follicular lymphoma that has come back after treatment with at least 2 previous therapies. The common side effects of copanlisib include high blood sugar, diarrhea, fatigue, high blood pressure, low white blood cell count, nausea, lung infections, and low blood platelet count.

Duvelisib (Copiktra) also targets the PI3K pathway. It is used to treat adults with small lymphocytic lymphoma that has not been stopped by at least 2 previous therapies. This targeted therapy is also used to treat chronic lymphocytic leukemia. The common side effects of duvelisib include diarrhea, intestinal problems, low white blood cell count, rash, fatigue, pain, cough, nausea, respiratory infection, pneumonia, pain, and anemia.

Ibrutinib (Imbruvica) targets the Bruton’s tyrosine kinase pathway. This drug is approved to treat several B-cell lymphomas, including mantle cell lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma, as well as chronic lymphocytic leukemia and Waldenström’s macroglobulinemia. Common side effects of ibrutinib include diarrhea, muscle and bone pain, rash, nausea, bruising, tiredness, and, less commonly, bleeding, irregular heartbeat (atrial fibrillation), or fever.

Immunotherapy

Immunotherapy, also called biologic therapy, is designed to boost the body's natural defenses to fight the cancer. It includes the monoclonal antibodies discussed above and uses effector cells and molecules made either by the body or in a laboratory to improve, target, or restore immune system function.

In chimeric antigen receptor (CAR) T-cell therapy, some T cells are removed from a patient’s blood. Then, the cells are changed in a laboratory so they have specific proteins called receptors. The receptors allow those T cells to recognize the cancer cells. The changed T cells are grown in large numbers in the laboratory and returned to the patient’s body. Once there, they seek out and destroy cancer cells.

Axicabtagene ciloleucel (Yescarta) is a CAR T-cell therapy that is approved to treat patients with DLBCL who have received at least 2 previous types of treatment. Tisagenlecleucel (Kymriah) is another CAR T-cell therapy that is approved for the treatment of refractory B-cell lymphoma, including DLBCL, after 2 previous systemic treatments or more. Further CAR T-cell therapies are in development and being studied in clinical trials.  

Different types of immunotherapy can cause different side effects. Talk with your doctor about possible side effects for the immunotherapy recommended for you. Learn more about the basics of immunotherapy.

Stem cell transplantation/bone marrow transplantation

A stem cell transplant is a medical procedure in which bone marrow or peripheral blood cells containing highly specialized cells, called hematopoietic stem cells, are used as part of a treatment plan. Hematopoietic stem cells are blood-forming cells found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than a bone marrow transplant. That’s because stem cells collected from the blood are typically being transplanted, not cells from the actual bone marrow tissue.

Stem cell transplantation is considered an aggressive treatment. It is generally used only for people with NHL whose disease is progressive or recurrent (see Stages). For some NHL subtypes, such as mantle cell lymphoma and some T-cell lymphomas, doctors may recommend stem cell transplantation as part of the initial treatment plan to prevent recurrence. Before recommending transplantation, the doctor will talk with the patient about the risks of this treatment. Doctors also consider several other factors, such as the type of NHL, results of any previous treatment, and patient’s age and general health. It is important to talk with a doctor at an experienced transplant center about the risks and benefits of stem cell transplantation.

There are 2 types of stem cell transplantation, depending on the source of the replacement blood stem cell: allogeneic (ALLO) and autologous (AUTO).

  • ALLO transplantation uses donated stem cells from a healthy individual, ideally a sibling or matched unrelated donor. Treatment includes immunochemotherapy, radiation therapy, or immunotherapy plus “graft versus lymphoma” activity, which is where the donor cells recognize and destroy the patient’s lymphoma cells. ALLO transplantation presents higher risks for patients than AUTO transplantation, including graft-versus-host disease, where donor cells damage the patient’s tissues or organs.

  • AUTO transplantation uses the patient’s own stem cells after high-dose chemotherapy. In AUTO transplantation, the goal is to destroy all of the cancer cells in the marrow, blood, and other parts of the body using high doses of chemotherapy, immunotherapy, and/or radiation therapy. The AUTO stem cells are returned to the patient’s body after the high-dose therapy is completed. The AUTO stem cells then work to create healthy bone marrow.

Side effects depend on the type of transplant, your general health, and other factors. Learn more about the basics of stem cell and bone marrow transplantation.

Getting care for symptoms and side effects

Lymphoma and its treatment often cause side effects. In addition to treatments intended to slow, stop, or eliminate the disease, an important part of care is relieving a person’s symptoms and side effects. This approach is called palliative or supportive care, and it includes supporting the patient with his or her physical, emotional, and social needs.

Palliative care is any treatment that focuses on reducing symptoms, improving quality of life, and supporting patients and their families. Any person, regardless of age or type and stage of cancer, may receive palliative care. It works best when palliative care is started as early as needed in the cancer treatment process. People often receive treatment for the lymphoma at the same time that they receive treatment to ease side effects. In fact, patients who receive both at the same time often have less severe symptoms, better quality of life, and report they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional support, and other therapies. You may also receive palliative treatments similar to those meant to eliminate the cancer, such as chemotherapy, surgery, or radiation therapy. Talk with your doctor about the goals of each treatment in your treatment plan.

Before treatment begins, talk with your health care team about the possible side effects of your specific treatment plan and palliative care options. During and after treatment, be sure to tell your doctor or another health care team member if you are experiencing a problem so it can be addressed as quickly as possible. Learn more about palliative care

Remission and the chance of recurrence

A complete remission is when lymphoma cannot be detected in the body and there are no symptoms. This may also be called having “no evidence of disease” or NED. Partial remission is when the lymphoma has regressed by more than 50% from its pre-treatment state but can still be detected.

A remission may be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. While many remissions are permanent, it’s important to talk with your doctor about the possibility of the disease returning. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the lymphoma does return. Learn more about coping with the fear of recurrence.

As explained in the Stages section, if the cancer does return after the original treatment, it is called recurrent cancer. It may come back in the same place (called a local recurrence), nearby (regional recurrence), or in another place (distant recurrence).

When this occurs, a new cycle of testing will begin again to learn as much as possible about the recurrence. In most cases, another tissue biopsy is needed to prove that the lymphoma has not changed or transformed into a more aggressive subtype. After this testing is done, you and your doctor will talk about your treatment options.

Treatment for recurrent NHL depends on 3 factors:

  • Where the cancer is and whether it has transformed into a more aggressive subtype

  • Type(s) of treatment given previously

  • Patient’s overall health

Often the treatment plan will include the treatments described above, such as chemotherapy, radiation therapy, targeted therapy, immunotherapy, or stem cell transplantation. However, they may be used in a different combination or given at a different pace. Your doctor may suggest clinical trials that are studying new ways to treat this type of recurrent cancer. Whichever treatment plan you choose, palliative care will be important for relieving symptoms and side effects.

People with recurrent cancer often experience emotions such as disbelief or fear. Patients are encouraged to talk with their health care team about these feelings and ask about support services to help them cope. Learn more about dealing with cancer recurrence.

Progressive NHL

Some patients with NHL may not experience a complete remission and will have small amounts of residual disease that is stable. Or, they’ll have residual disease that is actively growing despite treatment. If there is a small amount of residual disease that is stable, some patients with indolent NHL may be observed with watchful waiting for a period of time or be treated with monoclonal antibodies or other drugs. Local radiation therapy may also be a consideration. These patients may have breaks in treatment, sometimes lasting many years. If the lymphoma begins to grow or spread, this is called progression of disease, and active treatment will begin again.

It is important to understand that remission is not always possible in some indolent lymphomas. However, some patients can be safely monitored even if there is leftover disease. This is possible as long as there are no symptoms and the lymphoma has not affected blood counts or other organs.

For NHL patients with residual disease that is growing despite active treatment, see “Refractory NHL” below.

Refractory NHL

If standard treatments stop working well for NHL or the lymphoma comes back within 6 months after standard treatment, this is called refractory NHL. Patients with this diagnosis are encouraged to talk with doctors who are lymphoma experts to discuss options for the best treatment plan. Learn more about seeking a second opinion before starting treatment, so you are comfortable with the treatment plan chosen. This discussion may include clinical trials.

Treatment options for refractory NHL depend on 4 factors:

  • Where the cancer is

  • The lymphoma subtype

  • The type of treatment given previously

  • The patient’s overall health

The doctor may suggest chemotherapy, immunotherapy, stem cell transplantation, or a clinical trial. Palliative care will also be important to help relieve symptoms and side effects.

For most patients, a diagnosis of refractory NHL is very stressful and, at times, difficult to bear. Patients and their families are encouraged to talk about the way they are feeling with doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, including through a support group.

If treatment doesn’t work

Recovery from NHL is not always possible. If the cancer cannot be cured or controlled, the disease may be called advanced or terminal.

This diagnosis is stressful, and for many people, advanced cancer is difficult to discuss. However, people with advanced NHL, especially those with indolent lymphoma, may continue to live for a long time after a diagnosis of advanced cancer. It is important to have open and honest conversations with your doctor and health care team to express your feelings, preferences, and concerns. The health care team is there to help. Many team members have special skills, experience, and knowledge to support patients and their families. Making sure a person is physically comfortable and free from pain is extremely important.

Patients who have advanced cancer and who are expected to live less than 6 months may want to consider a type of palliative care called hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to talk with the health care team about hospice care options, which include hospice care at home, a special hospice center, or other health care locations. Nursing care and special equipment can make staying at home a workable option for many families. Learn more about advanced cancer care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.

The next section in this guide is About Clinical Trials. It offers more information about research studies that are focused on finding better ways to care for people with cancer. You may use the menu to choose a different section to read in this guide.