Lymphoma - Non-Hodgkin: Types of Treatment

Approved by the Cancer.Net Editorial Board, 03/2021

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

This section explains the types of treatments that are the standard of care for NHL. “Standard of care” means the best treatments known. When making treatment plan decisions, you 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. Clinical trials are an option to consider for treatment and care for all stages of cancer. Your doctor can help you consider all your treatment options. Learn more about clinical trials in the About Clinical Trials and Latest Research sections of this guide.

How NHL is treated

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, nurse practitioners, oncology nurses, social workers, pharmacists, counselors, dietitians, and others.

There are 4 main treatments for NHL:

  • Chemotherapy

  • Immunotherapy

  • Targeted therapy

  • Radiation therapy

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

The treatment of lymphoma is rapidly changing and has improved outcomes for many patients. It is important to have expert diagnostic confirmation of your subtype and to consider getting a second opinion regarding your treatment plan.

The common types of treatments used for NHL are described below. In addition, treatment for specific NHL subtypes is also provided. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care.

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

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. These types of talks are called "shared decision-making." Shared decision-making is when you and your doctors work together to choose treatments that fit the goals of your care. Shared decision-making is particularly important for NHL because there are different treatment options. 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, or 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.

Therapies using medication

Treatments using medication are used to destroy cancer cells. Medication may be given through the bloodstream to reach cancer cells throughout the body. When a drug is given this way, it is called systemic therapy. Medication may also be given locally, which is when the medication is applied directly to the cancer or kept in a single part of the body.

This type of medication is generally prescribed 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.

Medications are often given through an intravenous (IV) tube placed into a vein using a needle or as a pill or capsule that is swallowed (orally). If you are given oral medications, be sure to ask your health care team about how to safely store and handle it.

The types of medications used for NHL include:

  • Chemotherapy

  • Immunotherapy

  • Targeted therapy

Each of these types of therapies is discussed below in more detail. A person may receive 1 type of mediation at a time or a combination of medications given at the same time. They can also be given as part of a treatment plan that includes radiation therapy.

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.

It is also important to let your doctor know if you are taking any other prescription or over-the-counter medications or supplements. Herbs, supplements, and other drugs can interact with cancer medications, causing unwanted side effects or reduced effectiveness. Learn more about your prescriptions by using searchable drug databases.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. It is the main treatment for NHL.

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 a combination of different drugs given at the same time. The stage and type of NHL determines which chemotherapy is used. The most common chemotherapy combination for the first treatment of aggressive NHL is called CHOP and contains 4 medications:

  • Cyclophosphamide (available as a generic drug)

  • Doxorubicin (available as a generic drug)

  • Prednisone (multiple brand names)

  • Vincristine (Vincasar)

For patients with B-cell lymphoma, adding an anti-CD20 monoclonal antibody, such as rituximab (Rituxan) or obinutuzumab (Gazyva), to CHOP works better than using CHOP alone (see “Targeted therapy,” below). There are other common combinations of chemotherapy regimens, including:

  • BR, which includes bendamustine (Treanda) and rituximab

  • Combinations using fludarabine (available as a generic drug)

  • 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 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.

Immunotherapy

Immunotherapy, also called biologic therapy, is designed to boost the body's natural defenses to fight the cancer. This category of lymphoma treatments includes modified T cells and checkpoint inhibitors. It uses anti-lymphoma strategies to improve, target, or restore immune system function.

Chimeric antigen receptor (CAR) T-cell therapy. In CAR T-cell therapy, some T cells are removed from a patient’s blood. Then, the cells are modified in a laboratory so they have specific proteins called receptors. The receptors allow those T cells to recognize and immunologically destroy lymphoma cells that have the target protein. The changed T cells are grown in large numbers in the laboratory and returned to the patient’s body as a transfusion. 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 or recurrent or refractory follicular lymphoma who have received at least 2 previous types of treatment.

  • Tisagenlecleucel (Kymriah) is a CAR T-cell therapy that is approved for the treatment of refractory B-cell lymphoma, including DLBCL, after 2 or more previous systemic treatments.

  • Brexucabtagene autoleucel (Tecartus) is approved for adults with recurrent or refractory mantle cell lymphoma.

  • Lisocabtagene maraleucel (Breyanzi) is a CAR T-cell therapy approved for the treatment of adults with recurrent or refractory large B-cell lymphoma after 2 or more lines of systemic therapy. It can be used to treat DLBCL, not otherwise specified; high-grade B-cell lymphoma; primary mediastinal large B-cell lymphoma; and follicular lymphoma.

Further CAR T-cell therapies are in development and being studied in clinical trials. Learn more about the basics of CAR T-cell therapy.

Immune checkpoint inhibitors. This type of immunotherapy blocks specific pathways to stop or slow the growth of cancer. The PD-1 pathway is a target for several checkpoint inhibitors. One of these drugs, pembrolizumab (Keytruda), can be used to treat primary mediastinal large B-cell lymphoma.

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

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 and limits damage to healthy cells.

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, research studies continue to find out more about specific molecular targets and new treatments directed at them. Learn more about the basics of targeted treatments.

Targeted therapies used for NHL include monoclonal antibodies, kinase inhibitors, immunomodulatory drugs, and nuclear export inhibitors. Each category is described below in more detail. In general, monoclonal antibodies are the main form of targeted therapy used for many types of NHL. A monoclonal antibody recognizes and attaches to a specific protein and does not affect cells that do not have that protein. Some monoclonal antibodies are used to deliver an attached chemotherapy agent or toxin; these are called antibody-drug conjugates. Kinase inhibitors block a type of enzyme called a kinase. Kinases help control many functions in the body, and blocking kinases may stop or slow cancer growth. Immunomodulatory drugs modulate, or influence, how the body's immune system responds or works. The type of targeted therapy that may be recommended for your treatment plan depends on the type of NHL, the specific genetic changes in the lymphoma, and other factors.

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

Monoclonal antibodies

Rituximab (Rituxan). Rituximab is a targeted therapy used to treat many different types of B-cell NHL. It works by targeting a molecule called CD20 that is located on the surface of normal 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 generally works better when added to chemotherapy (see above) for patients with most types of B-cell NHL. Rituximab is also given after remission for indolent lymphoma to keep it from coming back.

There are 3 rituximab biosimilars that may be used to treat lymphoma: rituximab-abbs (Truxima), rituximab-arrx (Riabni), and rituximab-pvvr (Ruxience). These biosimilars function in a way very similar to rituximab, but they are different medications. Learn more about the basics of biosimilars.

Brentuximab vedotin (Adcetris). Brentuximab vedotin is an antibody-drug conjugate. Antibody-drug conjugates attach to targets on cancer cells and then release a small amount of chemotherapy or other toxin 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 the lymphoma expresses the CD30 protein.

Loncastuximab tesirine-lpyl (Zynlonta). Loncastuximab tesirine-lpyl is an antibody-drug conjugate that targets the CD19 protein. It is approved for the treatment of adults with certain subtypes of B-cell lymphoma that has not been stopped by 2 or more treatments.

Obinutuzumab (Gazyva). Obinutuzumab is a monoclonal antibody that targets CD20. It can be used in combination with bendamustine or by itself to treat follicular lymphoma that has come back after treatment with rituximab. It can also be used in combination with other chemotherapy to treat stage II bulky, stage III, and stage IV follicular lymphoma.

Ofatumumab (Arzerra). Ofatumumab is another monoclonal antibody that targets CD20. It may be used to treat small lymphocytic lymphoma.

Polatuzumab vedotin-piiq (Polivy). Polatuzumab is a monoclonal antibody that targets CD79b. Like brentuximab vedotin, it is also an antibody-drug conjugate. Polatuzumab is used in combination with rituximab, or bendamustine plus rituximab, to treat DLBCL that has come back after at least 2 other treatments.

Radiolabeled antibodies. Ibritumomab tiuxetan (Zevalin) is rituximab with radioactive isotopes attached. The isotopes 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 may be more damaging to the bone marrow. This type of therapy is also called radioimmunotherapy (RIT).

Tafasitamab-cxix (Monjuvi). This monoclonal antibody targets the CD19 molecule that is expressed on most normal B cells and B-cell lymphomas. It can be used in combination with lenalidomide (see "Immunomodulatory drugs" below) to treat recurrent or refractory DLBCL in those who cannot receive an autologous bone marrow/stem cell transplant (see below).

Research on the benefits of other newer monoclonal antibodies for lymphoma is ongoing.

Kinase inhibitors (updated 09/2021)

Ibrutinib (Imbruvica). Ibrutinib is a targeted therapy that targets the Bruton’s tyrosine kinase pathway. It 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 Waldenstrom macroglobulinemia. Common side effects of ibrutinib include diarrhea, muscle and bone pain, rash, nausea, bruising, tiredness, and, less commonly, bleeding, bruising, or irregular heartbeat (atrial fibrillation).

Acalabrutinib (Calquence). Acalabrutinib targets the Bruton’s tyrosine kinase pathway. It is approved to treat adults with mantle cell lymphoma and small lymphocytic lymphoma. The most common side effects of acalabrutinib are headache, diarrhea, muscle and join pain, upper respiratory tract infection, and bruising.

Zanubrutinib (Brukinsa). Zanubrutinib is another Bruton’s tyrosine kinase inhibitor. It is approved to treat mantle cell lymphoma and recurrent or refractory marginal zone lymphoma in people who have received at least 1 previous therapy. The common side effects of zanubrutinib are lowered white blood cell counts, lowered platelet count, upper respiratory tract infection, lowered hemoglobin levels, rash, bruising, diarrhea, and cough.

Copanlisib (Aliquopa). Copanlisib 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). Duvelisib 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 kinase inhibitor 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.

Idelalisib (Zydelig). Idelalisib is used to treat follicular lymphoma and small lymphocytic lymphoma/chronic lymphocytic leukemia that has come back after at least 2 previous therapies. Side effects include diarrhea, nausea, fatigue, increased liver enzymes, low blood counts, pneumonitis, intestinal perforation, and colitis.

Umbralisib (Ukoniq). Umbralisib targets the PI3K pathway. It is approved for adults with recurrent or refractory marginal zone lymphoma who have received at least 1 previous treatment with a monoclonal antibody that targets CD20. Umbralisib may also be used to treat adults with recurrent or refractory follicular lymphoma who have received at least 3 previous lines of systemic therapy.

Immunomodulatory drugs

Lenalidomide (Revlimid). Lenalidomide is a thalidomide analog used to treat follicular lymphoma and mantle cell lymphoma that have not been stopped by other treatments. This type of targeted therapy is also used to treat multiple myeloma and myelodysplastic syndromes.

EZH2 inhibitor

Tazemetostat (Tazverik). Tazemetostat is a targeted therapy that targets EZH2. The FDA has approved it for the treatment of follicular lymphoma that has come back after treatment or that has not been stopped by treatment. Adults with follicular lymphoma with an EZH2 mutation who have received 2 or more previous treatments with systemic therapy may receive tazemetostat. It may also be given to people who have no other available treatment options.

BCL2 inhibitor

Venetoclax (Venclexta). Venetoclax is a BCL2 inhibitor. This type of targeted therapy is used in combination with obinutuzumab as a first treatment for small lymphocytic lymphoma. Venetoclax may also be used in combination with rituximab. It is being studied in combinations with a Bruton's tyrosine kinase inhibitor as well as chemotherapy.

Nuclear export inhibitors

Selinexor (Xpovio). Selinexor is a drug that targets and blocks a protein called XPO1 in cancer cells. It is used to treat DLBCL that has come back or has not been stopped by 2 previous treatments, as well as DLBCL that has transformed from follicular lymphoma. Common side effects of selinexor include fatigue, nausea, decreased appetite, and diarrhea.

Before starting any cancer medication, talk with your doctor about possible side effects for a specific drug and how they can be managed.

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 people who have localized lymphoma, which means that it involves only 1 or 2 adjacent areas, or to people 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 people with advanced disease who have localized symptoms that can be relieved using radiation therapy, such as a painful bony lesion.

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 health 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 maintaining your sexual health and preserving fertility.

Radioimmunotherapy is a specialized form of targeted radiation treatment and is described in the monoclonal antibodies section above.

Learn more about the basics of radiation therapy.

Bone marrow/stem cell transplantation

A bone marrow 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 in the bloodstream and the bone marrow. This procedure is also called a stem cell transplant or hematopoietic stem cell transplant.

Transplantation is considered an aggressive treatment for NHL. 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 transplantation as part of the initial treatment plan to prevent or delay recurrence.

Before recommending transplantation, the doctor will talk with you about the risks of this treatment. Doctors also consider several other factors, such as the type of NHL, results of any previous treatment, and your age and general health. It is important to talk with an experienced doctor at a specialized transplant center about the risks and benefits of this treatment.

There are 2 types of bone marrow transplantation, depending on the source of the replacement hematopoietic stem cell:

  • Allogeneic (ALLO). 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.

  • Autologous (AUTO). 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 regenerate healthy bone marrow and normal blood cell production.

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

Physical, emotional, and social effects of cancer

Cancer and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.

Palliative care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of cancer, may receive this type of care. And it often works best when it is started right after a cancer diagnosis. People who receive palliative care along with treatment for the cancer often have less severe symptoms, better quality of life, and report that they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. You may also receive palliative treatments similar to those meant to get rid of the cancer, such as chemotherapy, surgery, or radiation therapy.

Before treatment begins, talk with your doctor about the goals of each treatment in the treatment plan being recommended. You should also talk about the possible side effects of the specific treatment plan and palliative care options. Many patients also benefit from talking with a social worker and participating in support groups. Ask your doctor about these resources, too.

During treatment, your health care team may ask you to answer questions about your symptoms and side effects and to describe each problem. Be sure to tell the health care team if you are experiencing a problem. This helps the health care team treat any symptoms and side effects as quickly as possible. It can also help prevent more serious problems in the future.

Learn more about the importance of tracking side effects in another part of this guide. Learn more about palliative care in a separate section of this website.

Treatment by type and subtype

These are general treatment options for the most common types and subtypes of NHL. Your doctor can help you consider all your individual treatment options. Keep in mind that treatment options are rapidly evolving as results from cancer research are reported. For information on a specific type of treatment, see the information above. For more information about specific stages of NHL, see the Stages section in this guide.

Indolent NHL

Because indolent lymphoma grows slowly, people diagnosed with this type of NHL may not need to start treatment when it is first diagnosed. Instead, watchful waiting may be recommended. In cases where there are many cancer cells in the body, called high-burden disease, treatment will be started even if there are no symptoms.

When indolent lymphoma is located only in 1 or 2 adjacent areas, it is called localized disease (stages I and II). For people with localized disease, radiation therapy is often used. However, most patients with indolent NHL have stage III or IV disease at the time of diagnosis. There are many effective treatments for these stages of indolent NHL, but it may come back months or years after treatment has finished and require more treatment.

Aggressive NHL

These types of lymphoma may develop rapidly, and treatment is usually started within weeks of diagnosis. Aggressive lymphomas usually need more intensive chemotherapy. The doctor may recommend adding radiation therapy to treat stage I or II disease or to treat lymphoma where the site of the disease is large, sometimes called “bulky” disease. Several forms of aggressive lymphoma may be cured with effective treatment.

Subtypes of B-cell lymphoma

DLBCL. About 2 out of 3 people with this aggressive lymphoma are cured with chemotherapy combined with the monoclonal antibody rituximab. There are several subtypes of DLBCL, some listed below, which have different prognoses and treatment approaches.

  • Chemotherapy

  • Radiation therapy, especially for lymphoma in a limited area or a bulky site of disease

  • Monoclonal antibodies, such as rituximab, polatuzumab, or tafasitamab-cxix

  • CAR T-cell therapy

  • Other targeted treatments

Follicular lymphoma. Early, stage I to stage II follicular lymphoma may be cured with radiation therapy. Bone marrow/stem cell transplantation may cure the disease in cases where the lymphoma comes back after initial chemotherapy as well as with some later recurrences. If follicular lymphoma transforms into DLBCL, it is usually treated the same way as DLBCL.

  • Watchful waiting, for lymphoma with a low tumor burden and no symptoms

  • Monoclonal antibody therapy, for advanced lymphoma with low tumor burden

  • Chemotherapy

  • Targeted therapy with a kinase inhibitor, monoclonal antibody, or lenalidomide

  • Immunotherapy with CAR T-cell therapy

  • Bone marrow/stem cell transplantation

Mantle cell lymphoma. For patients younger than 70, who are otherwise healthy, high-dose chemotherapy and AUTO bone marrow transplantation often results in the longest remission, and they may receive maintenance therapy. For older patients or those who are not able to receive an AUTO bone marrow transplant, maintenance therapy with rituximab is a standard treatment approach.

  • Chemotherapy

  • Monoclonal antibody, such as rituximab

  • Bone marrow/stem cell transplantation

  • Maintenance therapy with rituximab after initial treatment

  • Kinase inhibitors, such as acalabrutinib, ibrutinib, or zanubrutinib

  • Immunomodulatory drug, such as lenalidomide

  • CAR T-cell therapy with brexucabtagene autoleucel

Small lymphocytic lymphoma. People with small lymphocytic lymphoma/chronic lymphocytic leukemia may not require immediate treatment.

  • Watchful waiting

  • Kinase inhibitors, such as acalabrutinib, duvelisib, or ibrutinib

  • Monoclonal antibodies, such as obinutuzumab, rituximab, or venetoclax

  • Chemotherapy

Double hit/triple hit lymphoma. This is a subtype of DLBCL. There is currently no preferred treatment regimen for this type of aggressive lymphoma that has been confirmed in clinical trials.

  • Chemotherapy

  • Monoclonal antibodies, such as rituximab

Primary mediastinal large B-cell lymphoma. Most often, doctors treat this subtype of DLBCL with combination chemotherapy plus the monoclonal antibody rituximab. A closely related lymphoma called mediastinal grey-zone lymphoma (MGZL) is also treated in a manner similar to that of primary mediastinal large B-cell lymphoma.

  • Chemotherapy

  • Monoclonal antibody, such as rituximab

  • Radiation therapy

  • Immunotherapy with CAR T-cell therapy or the checkpoint inhibitor pembrolizumab

Splenic marginal zone B-cell lymphoma. Because this type of indolent lymphoma is usually slow-growing, the initial management approach is often watchful waiting.

  • Watchful waiting

  • Monoclonal antibody, such as rituximab

  • Chemotherapy

  • Surgery to remove the spleen

Extranodal marginal zone B-cell lymphoma of MALT (mucosa-associated lymphoid tissue).

  • Radiation therapy for disease only affecting 1 organ or site

  • Monoclonal antibody, such as rituximab

  • Chemotherapy

  • Antibiotics for gastric MALT caused by the Helicobacter pylori bacteria

Nodal marginal zone B-cell lymphoma. In general, doctors treat this subtype of lymphoma similarly to follicular lymphoma (see above).

Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia).

  • Watchful waiting

  • Chemotherapy

  • Bruton's tyrosine kinase inhibitors

  • Monoclonal antibodies

Learn more about the treatment of lymphoplasmacytic lymphoma and Waldenstrom macroglobulinemia.

Burkitt lymphoma/Burkitt cell leukemia. Burkitt lymphoma is often curable. Because it progresses and spreads quickly, it needs immediate treatment.

  • Chemotherapy plus rituximab, when given over several days, and typically given in a hospital for at least the beginning treatment cycle, can lead to long-term remission in more than 80% of patients

Subtypes of T-cell and NK-cell lymphoma

Anaplastic large cell lymphoma, primary cutaneous type.

  • Radiation therapy

  • Chemotherapy

  • Monoclonal antibody, such as brentuximab vedotin

Anaplastic large cell lymphoma, systemic type.

  • Chemotherapy

  • Monoclonal antibody, such as brentuximab vedotin

  • Bone marrow/stem cell transplantation

Breast implant-associated anaplastic large cell lymphoma.

  • Surgical removal of the implant

  • Chemotherapy in some cases

Peripheral T-cell lymphoma, not otherwise specified (NOS).

  • Chemotherapy

  • Bone marrow/stem cell transplantation

  • Monoclonal antibody, such as brentuximab vedotin

Angioimmunoblastic T-cell lymphoma.

  • Chemotherapy

  • Bone marrow/stem cell transplantation

Adult T-cell lymphoma/leukemia (human T-cell lymphotropic virus type I positive).

  • Immunotherapy with interferon

  • Zidovudine (Retrovir), an antiviral drug used to treat the human immunodeficiency virus (HIV)

  • Chemotherapy

  • Bone marrow/stem cell transplantation

Extranodal NK/T-cell lymphoma, nasal type. Radiation therapy in combination with chemotherapy is an important part of the treatment for disease that involves the nasal/sinus area.

  • Radiation therapy

  • Chemotherapy, usually including asparaginase (Elspar)

  • Bone marrow/stem cell transplantation

Enteropathy-associated T-cell lymphoma.

  • High-dose chemotherapy

  • Bone marrow/stem cell transplantation

Hepatosplenic T-cell lymphoma.

  • Chemotherapy

  • Bone marrow/stem cell transplantation

Primary cutaneous gamma/delta T-cell lymphoma. This is an aggressive disease treated similar to hepatosplenic T-cell lymphoma.

Subcutaneous panniculitis-like T-cell lymphoma. This disease often follows an indolent course.

  • Immunosuppressive medications, such as methotrexate (multiple brand names) or cyclosporine (multiple brand names)

  • Chemotherapy

  • Bone marrow/stem cell transplantation

Mycosis fungoides. Mycosis fungoides usually cannot be cured, but it is often manageable. In some centers, medical oncologists coordinate care with dermatologists and radiation oncologists to treat the disease and its related symptoms, which include rash and itching.

  • Topical medications

  • Radiation therapy

  • Controlled exposure to ultraviolet light or radiation therapy

  • Chemotherapy

  • Targeted therapy

  • Immunotherapy

  • Monoclonal antibodies, such as brentuximab vedotin and mogamulizumab (Poteligeo)

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 is 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 returns 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 the 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 before

  • The patient’s overall health

Often the treatment plan will include the treatments described above, such as chemotherapy, radiation therapy, targeted therapy, immunotherapy, or bone marrow/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 recurrent NHL. Whichever treatment plan you choose, palliative care will be important for relieving symptoms and side effects.

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

Progressive NHL

Some people with NHL may not experience a complete remission and will have small amounts of residual disease that is stable. Or, they will have residual disease that is actively growing despite treatment. Indolent NHL may be observed with watchful waiting for a period or be treated with targeted therapy or other drugs. Radiation therapy to the local area may also be a possibility. These patients may have breaks from 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 people can be safely monitored even if there is some remaining disease. This is possible as long as there are no symptoms and the lymphoma has not affected blood counts or other organs.

If there is residual disease that is growing despite active treatment, it is called "refractory NHL," see below.

Refractory NHL

If standard treatments stop working well for NHL or the lymphoma comes back within 6 months after treatment, this is called refractory NHL. People 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 chosen treatment plan. 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 before

  • The patient’s overall health

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

For most people, a diagnosis of refractory NHL is very stressful and difficult. You and your family are encouraged to talk about how you fell with doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, such as through a support group or other peer support program.

If treatment does not work

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

This diagnosis is stressful, and for some 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 health care team to express your feelings, preferences, and concerns. The health care team has special skills, experience, and knowledge to support patients and their families and is there to help. Making sure a person is physically comfortable, free from pain, and emotionally supported is extremely important.

People who have advanced cancer and who are expected to live less than 6 months may want to consider 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. Use the menu to choose a different section to read in this guide.