Treating B-Cell Non-Hodgkin Lymphoma
Diffuse large B-cell lymphoma
In most cases, the treatment for diffuse large B-cell lymphoma (DLBCL) is chemotherapy (chemo), usually with a regimen of 4 drugs known as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), plus the monoclonal antibody rituximab (Rituxan). This regimen, known as R-CHOP, is most often given in cycles 3 weeks apart.
Stage I or II
For DLBCL that is localized to 1 or 2 lymph node groups on the same side of the diaphragm, R-CHOP may be given for 3 cycles, followed by radiation therapy to the lymph node areas involved by lymphoma. If the lymphoma mass is large, R-CHOP may be given for 6 cycles, and radiation isn’t always needed.
Stage III or IV
Most doctors will give 6 cycles of R-CHOP as first-line treatment. Because CHOP contains the drug doxorubicin, which can damage the heart, this regimen may not be suitable for patients with heart problems. In those patients, other chemo regimens may be used instead. People with lymphoma in certain locations (such as the sinuses, testicles, or bone marrow) have a higher risk of the lymphoma coming back later in the tissues around the brain and spinal cord. To prevent that, these patients may be treated with chemo injected into the spinal fluid (called intrathecal chemotherapy). Another option is to give high doses of methotrexate intravenously (this drug can pass into the spinal fluid).
Some studies have suggested that for younger patients with a high International Prognostic Index (IPI) score, high-dose chemo followed by an autologous stem cell transplant may be better than chemo alone. But it’s not yet clear if transplants are better as the initial treatment. Most doctors feel that if a transplant is done as part of the first treatment, it should be done in a clinical trial.
If the lymphoma doesn’t go away completely with treatment or if it recurs (comes back) after treatment, doctors will usually suggest another chemo regimen. Several different regimens can be used, and they may or may not include rituximab. If the lymphoma shrinks with this treatment, it is followed by high-dose chemo and a stem cell transplant if possible, as it offers the best chance of curing the lymphoma. Stem cell transplants are not effective unless the lymphoma responds to chemo. Unfortunately, not everyone is in good enough health to have a stem cell transplant. Clinical trials of new treatments may be another good option for some people.
Diffuse large B-cell lymphoma can be cured in about half of all patients, but the stage of the disease and the IPI score can have a large effect on this. Patients with lower disease stages have better survival rates, as do patients with lower IPI scores.
Primary mediastinal B-cell lymphoma
This lymphoma is treated like a localized diffuse large B-cell lymphoma. The main treatment is usually about 6 courses of CHOP chemo plus rituximab (R-CHOP). This may be followed by radiation to the mediastinum. Often a PET/CT scan is done after the chemo to see if there’s any lymphoma remaining in the chest. If no active lymphoma is seen on the PET/CT, the patient may be observed without further treatment. If the PET/CT scan is positive (shows possible active lymphoma), radiation may be needed. Often, the doctor will order a biopsy of the chest tumor to confirm that lymphoma is still present before starting radiation.
This type of lymphoma is often slow growing and responds well to treatment, but it is very hard to cure. It is common for this lymphoma to come back after treatment, although it can take years to do so. In many cases, it is not clear that treating the lymphoma right away helps people live longer. Because of this, some doctors recommend no treatment until the lymphoma has begun to cause problems other than mildly swollen lymph nodes. Some patients may never need treatment at all. In those that do, it can take years before treatment is needed.
Stage I and early-stage II
For follicular lymphoma that is only in 1 lymph node group or in 2 nearby groups on the same side of the diaphragm, the preferred treatment is radiation therapy to the lymph node areas affected by lymphoma (this is called involved field radiation). Other choices include treatment with rituximab (Rituxan), chemo, or both (together).
Stages III, IV, and more advanced stage II
The most common treatment is rituximab combined with chemo. The chemo can be a single drug (such as bendamustine or fludarabine) or a combination of drugs, such as the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVP (cyclophosphamide, vincristine, prednisone) regimens. If the lymphoma shrinks, a total of 6 cycles of chemo plus rituximab is usually given. Other options for initial treatment include rituximab alone or chemo alone (either one or several drugs). If some lymph nodes are very large from the lymphoma, radiation may be used to reduce symptoms. This is most often used for patients who are too sick to be treated with chemo.
The radioactive monoclonal antibody ibritumomab (Zevalin) is also an option for initial treatment, although this is more often used as a second-line treatment.
For patients who may not be able to tolerate more intensive chemo regimens, rituximab alone, milder chemo drugs (such as chlorambucil or cyclophosphamide), or both may be good options.
If the lymphoma shrinks or goes away with the initial treatment, doctors may advise either close follow-up or further treatment. This might include either rituximab for up to 2 years or treatment with ibritumomab. Further treatment may lower the chance that the lymphoma will come back later and may help some patients live longer, but it can also have side effects.
If follicular lymphoma doesn’t respond to the initial treatment or if it comes back later, it may be treated with different chemo drugs, targeted drugs, monoclonal antibodies, or some combination of these. If the lymphoma responds to this treatment, a stem cell transplant may be an option.
In some cases, follicular lymphoma can change (transform) into or return as diffuse large B-cell lymphoma. When this happens, the treatment is the same as for this more aggressive disease.
Small lymphocytic lymphoma (and chronic lymphocytic leukemia)
Small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL) are considered different versions of the same disease. The main difference is where the cancer cells are – the blood and bone marrow for CLL and the lymph nodes and spleen for SLL. CLL and SLL tend to grow slowly, but are very hard to cure.
Treatment for SLL is similar to that of CLL, which is described in detail in Chronic Lymphocytic Leukemia.
If the lymphoma isn’t growing quickly or causing any problems, it can be watched closely without treatment for a time.
If treatment is needed, it depends on the stage. When the lymphoma is only in one lymph node or lymph node area (Ann Arbor stage I), it may be treated with radiation treatment alone.
For more advanced disease, the treatment is often the same as what is used for CLL (this is discussed in detail in Chronic Lymphocytic Leukemia). Chemo, with or without rituximab or obinutuzumab (Gazyva) is the usual first-line treatment. Chlorambucil, fludarabine, or bendamustine are some of the chemo drugs that are used. Another option is to give rituximab alone (without chemo). Which treatment is used depends on the age and health of the patient, as well as on whether the cancer cells have certain chromosome changes.
If the lymphoma doesn’t respond or comes back after initial treatment, different chemo drugs, targeted drugs, and/or other monoclonal antibodies may be used as second-line treatment.
Mantle cell lymphoma
This type of lymphoma is very hard to cure. It has often spread widely when it’s first found, and although it doesn’t usually grow as quickly as some other fast-growing lymphomas like Burkitt lymphoma, it often doesn’t respond as well to treatment, either. Because current treatments for this type of lymphoma are very unlikely to cure it, patients might want to consider taking part in a clinical trial.
If the lymphoma has only spread to 1 lymph node group or to 2 nearby groups on the same side of the diaphragm (stage I and some stage II – which is rare), it can sometimes be treated with radiation therapy. Another option is to treat with chemo plus rituximab.
Cases of mantle cell lymphoma that are more widely spread when they are first diagnosed are treated with chemo plus rituximab. When possible, the chemo treatment is intense, such as
- Hyper-CVAD: cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dexamethasone, alternating with high-dose methotrexate plus cytarabine).
- “Dose-intensified” CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) alternating with rituximab and cytarabine.
- CHOP plus rituximab followed by rituximab plus ifosfamide, carboplatin, and etoposide (known as ICE)
Less intense chemo regimens may be used for people who are older or who have other health issues.
For those whose lymphoma responds well to initial treatment, a stem cell transplant may be a good option.
For mantle cell lymphomas that don’t respond or that come back after initial treatment, chemo with drugs such as bendamustine, bortezomib (Velcade), cladribine, fludarabine, lenalidomide (Revlimid), or ibrutinib (Imbruvica) may be used, sometimes along with other chemo drugs or with rituximab. Still, because the outlook for patients with these lymphomas is poor with second-line treatment (treatment given after the first treatment didn’t work), they should consider entering a clinical trial.
Extranodal marginal zone B-cell lymphoma – mucosa-associated lymphoid tissue (MALT) lymphoma
The most common type, gastric (stomach) MALT lymphoma, often occurs as a result of a chronic infection with the bacterium, H. pylori and can respond if the infection is treated. Because of this, gastric lymphomas are treated differently from other lymphomas in this group.
Stages I and II in people who tested positive for H. pylori:
Early-stage gastric MALT lymphomas, are treated with antibiotics combined with drugs that block acid secretion by the stomach called proton pump inhibitors. Usually the drugs are given for 10 to 14 days. This may be repeated after a couple of weeks. Examination of the stomach lining using upper endoscopy (where a flexible tube with a viewing lens is passed down the throat through the esophagus and into the stomach) is then repeated at certain intervals to see if the H. pylori is gone and if the lymphoma has decreased in size. About 2 out of 3 of these lymphomas go away completely with antibiotic treatment, but it can sometimes take several months to be effective. In cases where symptoms need to be relieved before the antibiotics take effect or where antibiotics don’t shrink the lymphoma, radiation therapy to the area is often the preferred treatment. The monoclonal antibody rituximab may be another option.
Stages I and II in people who test negative for H. pylori
For these early-stage gastric MALT lymphomas, treatment is usually either radiation therapy to the stomach or rituximab.
Stage III or IV
For more advanced gastric MALT lymphomas, which are rare, treatment is often similar to that for follicular lymphoma (see above). Lymphomas that are not growing quickly may be watched and not treated right away. If the lymphoma is large, is causing symptoms, or is growing, it can be treated with radiation therapy to the stomach, rituximab, chemo, or chemo plus rituximab. The drugs used are the same as those used for follicular lymphoma, and may include single agents such as chlorambucil or fludarabine or combinations such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVP (cyclophosphamide, vincristine, prednisone).
For MALT lymphomas that start in sites other than the stomach (non-gastric lymphomas), treatment depends on the location of the lymphoma and how much it has spread. Early-stage lymphomas can often be treated with radiation to the area containing the lymphoma. In certain sites (such as the lungs, breast, or thyroid), surgery may be an option. For more advanced disease (stage III or IV), treatment is generally the same as for stage III and IV gastric MALT lymphoma and follicular lymphoma (see above).
Nodal marginal zone B-cell lymphoma
This rare type of lymphoma generally grows slowly. Like follicular lymphoma, it often does not need to be treated at first. If treatment is needed, what is used depends upon the stage of the lymphoma.
Stage I and early-stage II
If the lymphoma is only in 1 lymph node group or in 2 nearby groups on the same side of the diaphragm, the preferred treatment is radiation therapy to the lymph node areas affected by lymphoma (this is called involved field radiation). Other choices include treatment with rituximab (Rituxan), chemo, or both (together).
Stages III, IV, and more advanced stage II:
The most common initial treatment is rituximab combined with chemo. The chemo can be a single chemo drug (such as bendamustine or fludarabine) or a combination of drugs, such as the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVP (cyclophosphamide, vincristine, prednisone) regimens. If the lymphoma shrinks, a total of 6 cycles of chemo plus rituximab is usually given.
Other options for initial treatment include rituximab alone or chemo alone (either one or several drugs). If some lymph nodes are very large from the lymphoma, radiation may be used to reduce symptoms. This is most often used for patients who are too sick to be treated with chemo.
The radioactive monoclonal antibody ibritumomab tiuxetan (Zevalin) is also an option for initial treatment, although this is more often used as a second treatment.
For patients who may not be able to tolerate more intensive (stronger) chemo regimens, rituximab alone, milder chemo drugs (such as chlorambucil or cyclophosphamide), or both may be good options.
If the lymphoma shrinks or goes away with the initial treatment, doctors may advise either close follow-up or further treatment. This might include either rituximab for up to 2 years or treatment with ibritumomab tiuxetan. Further treatment may lower the chance that the lymphoma will come back later and may help some patients live longer, but it can also have side effects.
If the lymphoma doesn’t respond to the initial treatment or if it comes back later, it may be treated with different chemo drugs, monoclonal antibodies, or some combination of these. If the lymphoma responds to this treatment, a stem cell transplant may be an option.
Nodal marginal zone B-cell lymphoma can also change into a fast-growing large cell lymphoma, which would require more aggressive chemotherapy.
Splenic marginal zone B-cell lymphoma
This is also a slow-growing lymphoma. If it is not causing symptoms, it is often watched closely without treating it right away. For a patient with chronic hepatitis C virus infection, treating the infection with interferon with or without anti-viral drugs can cause the lymphoma to go into remission.
If that doesn’t work and for people who aren’t infected with hepatitis C, removing the spleen with surgery can sometimes lead to a long-term remission of the disease. This can be very helpful in relieving symptoms if the spleen is enlarged. Treatment with rituximab may be another option.
If the disease is more advanced or progresses, it’s usually treated with chemo with or without rituximab.
Sometimes this lymphoma can transform into an aggressive large-cell lymphoma, which then requires more intensive chemo.
This is a very fast-growing lymphoma that is similar to a type of acute lymphocytic leukemia. It is usually treated in the hospital with intensive chemo. Most regimens for this disease include at least 5 chemo drugs. Many regimens also include a steroid drug such as prednisone or dexamethasone. Rituximab may also be added. Some examples of chemo regimens used for this lymphoma include:
- Hyper-CVAD: cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dexamethasone, alternating with methotrexate and cytarabine (ara-C)
- CODOX-M/IVAC: cyclophosphamide, vincristine (Oncovin), doxorubicin, and high-dose methotrexate, alternating with ifosfomide, etoposide (VP-16), and cytarabine (ara-C).
- EPOCH: etoposide, prednisone, vincristine (Oncovin), cyclophosphamide, and doxorubicin
Because this lymphoma tends to invade the area around the brain and spinal cord, the chemo drug methotrexate is often given into the spinal fluid (this is called intrathecal therapy). This may not be needed if high-dose methotrexate is given as a part of systemic chemotherapy.
An important part of the initial treatment of this disease is making sure these patients get plenty of fluids and drugs like allopurinol to help prevent tumor lysis syndrome (described in Chemotherapy for Non-Hodgkin Lymphoma).
If the lymphoma doesn’t respond or comes back after treatment, other chemo may be tried. If the lymphoma goes into remission, the doctor might suggest a stem cell transplant.
Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia)
Hairy cell leukemia
This is a slow-growing lymphoma that tends to invade the spleen and lymph nodes as well as the blood. Patients without symptoms often don’t need to be treated right away. When treatment is needed, most often the chemo drugs cladribine (2-CdA) or pentostatin are used. For more detailed information see Chronic Lymphocytic Leukemia.
Primary central nervous system (CNS) lymphoma
This lymphoma begins in the brain or spinal cord. It often develops in older people or those with immune system problems caused by AIDS or drugs given to keep transplanted organs from being rejected.
Most patients are treated with chemo and/or radiation. One problem with treating this disease is that most chemo drugs commonly used to treat lymphoma don’t reach the brain when given intravenously (IV). For people in reasonably good health, high IV doses of the drug methotrexate have been shown to be the most effective treatment. This is given along with the drug leucovorin and IV fluids, which help limit serious side effects. Other chemo drugs, such as cytarabine, may be added. Rituximab may be added as well. For those who aren’t able to tolerate this treatment, other, less intensive chemo regimens or radiation therapy alone may be tried.
One problem with radiation therapy, especially in older patients, is that it often causes mental changes. Doctors limit the dose of radiation to try to lessen this problem.
If CNS lymphoma keeps growing or comes back after treatment, further options may include chemo (using different drugs), radiation therapy, or a stem cell transplant if a person is healthy enough.
Historically, the outlook for patients with primary CNS lymphoma has not been as good as for other lymphomas, but this is at least partly related to the fact that they tend to be older or have other serious health problems.
Treatment of lymphoma of the eye (primary intraocular lymphoma) is discussed in Eye Cancer (Melanoma and Lymphoma).
Freedman AS, Jacobson CA, Mauch P, Aster JC. Chapter 103: Non-Hodgkin’s lymphoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.
Roschewski MJ, Wilson WH. Chapter 106: Non-Hodgkin Lymphoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa: Elsevier; 2014.
Last Medical Review: August 26, 2014 Last Revised: February 29, 2016
- Chemotherapy for Non-Hodgkin Lymphoma
- Immunotherapy for Non-Hodgkin Lymphoma
- Targeted Therapy Drugs for Non-Hodgkin Lymphoma
- Radiation Therapy for Non-Hodgkin Lymphoma
- High-Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin Lymphoma
- Surgery for Non-Hodgkin Lymphoma
- Palliative and Supportive Care for Non-Hodgkin Lymphoma
- Treating B-Cell Non-Hodgkin Lymphoma
- Treating T-Cell Non-Hodgkin Lymphomas
- Treating HIV-Associated Lymphoma
- What Should You Ask Your Doctor About Non-Hodgkin Lymphoma?