by Dr. C.H. Weaver M.d. updated 10/2021
A Marginal zone lymphomas (MZL) involve immune cells known as B cells, and account for between 5% and 17% of all non-Hodgkin lymphomas. The three main subtypes of MZL are extra-nodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), nodal MZL, and splenic MZL. Of these, MALT lymphoma is the most common.1
MZL primarily affects adults, and roughly half of people with MZL are over the age of 60 at the time of diagnosis. The symptoms that may be caused by MZL depend on the type and location of the MZL. MALT lymphoma commonly involves the stomach, and patients may report abdominal pain, heartburn, and indigestion. MALT lymphoma may also develop in other areas of the body, such as the area around the eye, the salivary glands, or the lungs.2 Splenic MZL may be detected because of enlargement of the spleen or abnormal blood cell counts.3 These types of lymphoma tend to be indolent (slow growing).
Diagnosis and Staging
If lymphoma is suspected, patients will usually have a biopsy performed. A biopsy involves the removal and examination of a sample of affected tissue. It allows a doctor to determine the presence and type of lymphoma. A diagnostic workup may also involve a physical exam, blood tests, and imaging scans.
If the biopsy confirms a diagnosis of MZL, patients may undergo additional tests and imaging scans to determine the extent (stage) of the disease.
Treatment of Marginal Zone Lymphomas
Treatment depends on the type and location of the MZL and may consist of radiation therapy or systemic treatment with chemotherapy, immunotherapy or precision cancer medicines targeting the b cells. Treatment options have expanded greatly in recent years and several innovative and effective treatments are in development. Although treatment can be administered effectively by community oncologists, patients should strongly consider a second opinion by a lymphoma expert at a major cancer center.
Treatment of MALT Lymphoma
Gastric (stomach) MALT lymphoma
Many cases of gastric (stomach) MALT lymphoma are the result of chronic infection with a bacterium known as Helicobacter pylori (H. pylori). For patients with early-stage gastric MALT lymphoma who test positive for this infection, use of antibiotics to eliminate the infection often provides effective lymphoma treatment.(4) To evaluate treatment response, your doctor will likely perform an endoscopy (a procedure that involves the use of a scope to view the inside of your stomach) a few months after treatment. Antibiotic treatment may be less effective for lymphomas that contain certain genetic changes, and your doctor may test for these genetic changes prior to starting treatment.
For early-stage gastric MALT lymphomas that test negative for H. Pylori (or that do not respond to treatment with antibiotics), treatment often involves radiation therapy. Chemotherapy and/or Rituxan® (rituximab) are also options for some patients. Rituxan is a type of drug known as a monoclonal antibody. It recognizes and binds to a protein (CD20) found on the surface of B cells, including the cancerous B cells of MZL. The binding of Rituxan to the B cell prompts the immune system to destroy the cell, and may also have direct anticancer effects on the cell.
Advanced-stage gastric MALT lymphoma is less common. Depending on whether or not the condition is causing symptoms, treatment may involve observation, use of chemotherapy and/or Rituxan, or participation in a clinical trial. Clinical trials are studies that evaluate the effectiveness and safety of new cancer drugs or cancer treatment strategies. Good sources of information about ongoing clinical trials include the patient’s cancer treatment team and the website of the National Cancer Institute.
Non-gastric MALT lymphoma
Although the stomach is the most common location of MALT lymphoma, the condition can also involve many other parts of the body. Treatment of early-stage MALT lymphoma in these other sites may involve radiation therapy, surgery, or observation. Some cases may be candidates for chemotherapy and/or immunotherapy (with a drug such as Rituxan) or participation in a clinical trial.
Splenic MZL that is not causing symptoms can often be managed with observation, and patients may experience stable disease without treatment for many years.3
Some cases of splenic MZL are linked with hepatitis C virus (HCV) infections, and treatment of HCV can provide a benefit. Other treatments that may be used for splenic MZL include splenectomy (surgical removal of the spleen) or Rituxan.
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The use of Rituxan was reported in a small number of patients with Splenic MZL.5
- A complete or partial disappearance of detectable lymphoma was experienced by 88% of patients treated with Rituxan alone, 83% of patients treated with Rituxan and chemotherapy, and 55% of patients treated with chemotherapy alone.
- The proportion of patients who survived for three years or longer was 95% among patients treated with Rituxan alone, 100% among patients treated with Rituxan and chemotherapy, and 55% among patients treated with chemotherapy alone.
The researchers conclude that among patients with splenic marginal zone lymphoma or marginal zone lymphoma, treatment that includes Rituxan appears to produce better outcomes than treatment with chemotherapy alone.
Nodal MZL is a rare condition. The Guidelines panel of the National Comprehensive Cancer Network recommends that nodal MZL be treated according to the guidelines for follicular lymphoma (another indolent type of NHL).5 Treatment may involve radiation therapy, chemotherapy, Rituxan, observation, or participation in a clinical trial.
In addition to Rituxan other B cell directed therapies are used to treat MZL.
Rituxan + Revlimid
In another trial patients with stage III/IV MZL were treated with Revlimid (lenalidomide) 20 mg daily on days 1 to 21 and Rituxan on day 1 of each 28-day cycle for ≥ 6 to 12 cycles.
Overall 93% of individuals responded to treatment and 70% of patients achieved a complete remission for a 5 - year survival rate of 96%. The most significant side effect was neutropenia occurring in 1/3 of patients.7
In May 2019, the Food and Drug Administration approved Revlimid® + Rituxan for previously treated MZL patients based on results of the AUGMENT trail which compared Revlimid + Rituxan to Rituxan alone. The average time to cancer progression was 39.4 months for the combination compared to only 14.1 months for Rituxan alone.
Side effects occurred with the most common being neutropenia, fatigue, diarrhea, constipation, nausea, and cough which occurred in at least 20% of patients.8
Imbruvica® works by blocking a specific protein called Bruton’s tyrosine kinase (BTK). The BTK protein transmits important signals that tell B cells to mature and produce antibodies and is needed by specific cancer cells to multiply and spread. Imbruvica® targets and blocks BTK, inhibiting cancer cell survival and spread.
The FDA approval was based on results from a clinical trial assessing the safety and effectiveness of Imbruvica® in 63 patients with MZL who received at least one prior therapy, including all 3 subtypes: mucosa-associated lymphoid tissue (MALT; n=32), nodal MZL (NMZL; n=17), and splenic MZL (SMZL; n=14). One in 4 patients treated experienced a response to treatment and 3.2% of patients achieved a complete remission. The median time to initial response was 4.5 months and the median duration of response had not been reached with median follow-up of 19.4 months.6,9
- Thieblemont C. Clinical presentation and management of marginal zone lymphomas. Hematology Am Soc Hematol Educ Program. 2005:307-13.
- Troch M, Kiesewetter B, Raderer M. Recent developments in nongastric mucosa-associated lymphoid tissue lymphoma. Curr Hematol Malig Rep. 2011; 6:216-221.
- Thieblemont C, Davi F, Noguera M-E, Briere J. Non-MALT marginal zone lymphoma. Curr Opin Hematol. 2011;18:273-279.
- Stathis A, Bertoni F, Zucca E. Treatment of gastric marginal zone lymphoma of MALT type. Expert Opin Pharmacother. 2010; 11:2141-2152
- Tsimberidou AM, Catovsky D, Schlette E et al. Outcomes in Patients with Splenic Marginal Zone Lymphoma and Marginal Zone Lymphoma Treated with Rituximab with or without Chemotherapy or Chemotherapy Alone. Cancer. 2006;107:125-35.
- IMBRUVICA U.S. Prescribing Information, December 2016.
- British Journal of Haematology (2019 Mar 28. Epub ahead of print).
- FDA approves lenalidomide for follicular and marginal zone lymphoma
- 58th Amer Society of Hematology Meeting; (Abstract #1213