Indolent non-Hodgkin lymphoma (NHL) subtypes progress slowly. They make up about 40 percent of all NHL cases in the United States. Indolent subtypes include:
- Cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome)
- Follicular lymphoma (FL)
- Lymphoplasmacytic lymphoma and Waldenström macroglobulinemia
- Marginal zone lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma
- Small cell lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL)
Treatment for indolent NHL ranges from observation with careful monitoring (the watch-and-wait approach) to aggressive therapy. Indolent NHL management or treatment is highly individual. Your doctor considers a number of factors such as:
- Prognostic factors
- Stage of disease
- Age and other medical conditions.
Treating Specific Indolent Subtypes
Cutaneous T-cell lymphomas (CTCLs) are a group of NHLs that develop primarily in the skin and may grow to involve lymph nodes, blood and other organs. This type of lymphoma originates in a T-cell. Mycosis fungoides is the most common type of CTCL, and is characterized by prominent skin involvement. When the malignant lymphocytes enter and accumulate in the blood, the disease is called Sézary syndrome.
Therapy for CTCL depends on the nature of the skin lesions and whether disease is present in the lymph nodes. Topical therapies are among the approaches used to treat the skin lesions. These include drugs applied directly to the skin combined with either ultraviolet light therapy or electron beam therapy. Ultraviolet light is used in conjunction with psoralen (a drug that becomes active when it is exposed to light); the combination therapy is often referred to as “PUVA” (psoralen and ultraviolet A) therapy.
If there is widespread involvement of lymph nodes and other sites, single- or multi-drug chemotherapy or extracorporeal photopheresis can be used. Extracorporeal photopheresis (ECP) is a method of removing blood from the body and treating it with ultraviolet light before returning it to the body. This treatment is recommended for patients either with, or at risk for, blood involvement such as that seen in Sézary syndrome.
To read more about cutaneous T-cell lymphoma and treatment options, download or order The Leukemia & Lymphoma Society's (LLS's) free fact sheet Cutaneous T-Cell Lymphoma Facts.
Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL), making up about 20 percent of all NHL cases. Most patients with FL are age 50 or older at diagnosis. Most follicular lymphoma cells have a specific chromosomal abnormality (a translocation between parts of chromosomes 14 and 18) that causes the production (overexpression) of the gene, BCL-2, which can make the cells resistant to therapy.
FL is a very slow-growing disease. Some patients may not need treatment for several years, whereas others may have extensive lymph node or organ involvement and need treatment right away. In a small percentage of patients, FL may transform into a more aggressive disease.
Stage I or stage II FL may be treated with:
- Watch-and-wait approach; patients with less advanced disease can be observed with periodic examinations and imaging tests.
- Radiation therapy
- Chemotherapy with rituximab (Rituxan®) followed by radiation therapy
For patients with stage II FL who have large lymph nodes, stage III or stage IV FL or advanced-stage relapsed FL, treatment will be based on symptoms, the patient's age and health status and the extent of the patient's disease. Taking part in a clinical trial can also be a good treatment option. Other treatment options include
- Radiation therapy to lymph nodes that are causing symptoms, or to a large localized mass, if one is present
- Single chemotherapy drugs in combination with rituximab. Examples of drugs used for treatment include cyclophosphamide (Cytoxan®), chlorambucil (Leukeran®) or bendamustine (Bendeka™)
- Chemotherapy combinations plus rituximab, such as R-CVP (rituximab plus cyclophosphamide, vincristine [Oncovin®], and prednisone) or R-CHOP (rituximab plus cyclophosphamide, hydroxydoxorubicin [doxorubicin], vincristine and prednisone)
- A radioactive monoclonal antibody, such as yttrium-90+ibritumomab tiuxetan (Zevalin®)
- Stem cell transplantation for some patients
- Idelalisib (Zydelig®) to treat patients who have relapsed FL and who have received at least two prior therapies.
Doctors have created a scoring system called the Follicular Lymphoma International Prognostic Index that is used to predict which patients have a higher risk of the disease returning (recurring). Doctors design a treatment plan based upon the patients' score. Factors that raise the risk for FL patients include:
- Older than 60
- Stage III or IV disease
- More than five lymph nodes involved
- An elevated level of lactic dehydrogenase (a type of protein) in the blood
- Hemoglobin concentration less than 12 g/dL.
Lymphoplasmacytic lymphoma and Waldenström macroglobulinemia are both slow-growing types of lymphoma that originate in a B-lymphocyte precursor. Both subtypes can become more advanced and involve the lungs, the gastrointestinal tract and other organs.
One option for patients without symptoms is to take a watch-and-wait approach. Active treatment begins for patients only if symptoms develop. Therapy regimens may then include a combination of biological agents (monoclonal antibodies such as rituximab), signaling inhibitors (drugs that block cell growth and survival signals), and chemotherapy with alkylating agents such as chlorambucil (Leukeran®), melphalan (Alkeran®) and cyclophosphamide (Cytoxan®). The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica®) has been approved by the FDA for the treatment of patients with symptomatic Waldenström macroglobulinemia.
A serious complication of both diseases is called hyperviscosity syndrome. Hyperviscosity syndrome may occur when the malignant cells secrete an abnormal protein that can thicken the blood. This leads to inadequate blood flow, causing such symptoms as headache, blurred vision and mental confusion. Hyperviscosity syndrome can be treated with plasmapheresis, a process of removing plasma from the blood. This is followed by treatment to control the lymphoma.
For more about Waldenström macroglobulinemia and treatment options, download or order LLS's free fact sheet Waldenström Macroglobulinemia Facts.
Marginal zone lymphoma can develop in either the lymph nodes (nodal) or outside the lymph nodes (extranodal). It begins in B lymphocytes in a part of the lymph tissue called the "marginal zone." The disease tends to remain localized.
Marginal zone lymphoma includes several subtypes, each categorized by the type of tissue where the lymphoma forms.
- Gastric mucosa-associated lymphoid tissue (MALT) lymphoma usually develops in the stomach. Patients with MALT lymphoma may have a history of an autoimmune disease such as Hashimoto thyroiditis or Sjögren syndrome. A higher incidence of MALT lymphoma involving the stomach is seen in patients who have been infected with the bacterium H. pylori. Bacteria have also been implicated in other forms of MALT lymphoma. Treatment often includes potent combinations of antibiotics, which both eradicate the H. pylori infection and cause the lymphoma to regress. Many patients with H. pylori have been cured of MALT lymphoma without radiation or chemotherapy. For a small subset of patients, MALT lymphoma can transform into diffuse large B-cell lymphoma (DLBCL). These patients can benefit from treatments used for DLBCL. See Diffuse Large B-cell Lymphoma.
- Extragastric MALT lymphoma begins outside the stomach and may form in almost any part of the body including other areas of the GI tract, salivary glands, thyroid, lung, skin and around the eye.
- Monocytoid B-cell lymphoma, also known as “nodal marginal zone B-cell lymphoma,” may be found in the spleen and blood. This form of NHL is generally treated like follicular lymphoma. See Follicular Lymphoma.
- Splenic marginal zone lymphoma (SMZL) begins in the spleen and may spread to the blood and bone marrow. One of the first signs of SMZL is an enlarged spleen; however, symptoms can be slow to develop. SMZL has been associated with hepatitis C infection. Treatment for hepatitis C with interferon (either alone or in combination with ribavirin) may result in a remission of the patient’s lymphoma.
For patients with SMZL who do not have hepatitis C or any symptoms of lymphoma, the first treatment may be the watch-and-wait approach. Treatment is generally started when an enlarged spleen starts to cause symptoms or produces low white blood cell counts. For symptomatic patients who are hepatitis-C negative, treatment may include
- Removal of the spleen
- Single-agent chemotherapy
- Combination chemotherapy
- Immunotherapy with rituximab
- Rituximab combined with chemotherapy.
Small cell lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL) are similar NHL subtypes. They tend to affect the same age groups (median age of patients is 65 years), have common signs and symptoms and be slow-growing. The differences lie in where they develop: SLL mostly affects the lymph nodes and lymphoid tissue; CLL mostly affects blood and bone marrow but can spread to the lymph nodes.
Rituximab or a rituximab-containing regimen is used as first-line therapy for CLL/SLL . The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica®) has also been approved as first-line therapy. The PI3K inhibitor idelalisib (Zydelig®) in combination with rituximab and the BCL-2 inhibitor venetoclax (Venclexta®) have been approved for use in patients with relapsed CLL/SLL. Bendamustine hydrochloride is a chemotherapy agent that has been approved for the treatment of CLL patients who have progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.
To read more about CLL and its treatment options, download or order LLS's free booklet Chronic Lymphocytic Leukemia.