Marginal Zone Lymphoma: Relapsed and Refractory Disease
When marginal zone lymphoma returns after treatment or stops responding to therapy, patients face a challenging situation that requires specialized care and new treatment approaches.
Table of contents
- What is Relapsed/Refractory Marginal Zone Lymphoma?
- Prognosis and Survival
- Treatment Options
- Targeted Therapies
What is Relapsed/Refractory Marginal Zone Lymphoma?
Marginal zone lymphoma is the second most common type of slow-growing B-cell non-Hodgkin’s lymphoma, which is a cancer that develops from white blood cells called lymphocytes. It accounts for 5 to 15 percent of all non-Hodgkin’s lymphoma cases.[1]
The term relapsed describes disease that comes back or starts growing again after a period when it could not be detected. The term refractory is used when the lymphoma does not respond to treatment, meaning the cancer cells continue to grow, or when the response to treatment does not last very long.[2]
Although many patients achieve long-lasting control of their disease after initial treatment, the lymphoma can return. About 20 percent of patients with marginal zone lymphoma experience relapse or disease progression within 2 years of starting treatment.[1]
Prognosis and Survival
Patients with marginal zone lymphoma typically have a long survival period, with a median survival of more than 10 years. When treated with a combination that includes an anti-CD20 monoclonal antibody (a type of targeted therapy that attacks a specific protein on lymphoma cells), patients can achieve an overall response rate of 81 percent.[1]
However, patients who experience relapse or progression within 2 years face a more difficult situation. These patients have a median survival of only 3 to 5 years, which is significantly shorter than those who maintain longer remissions.[1]
Treatment Options
For patients who need treatment for relapsed or refractory disease, the same therapies used for newly diagnosed patients can often be used. Treatment selection is based on several factors, including the patient’s age, overall health, symptoms, and how long the remission lasted after the previous treatment.[2]
Currently, treatment options for patients with relapsed or refractory marginal zone lymphoma are limited, which highlights the urgent need for new therapeutic approaches.[1]
Commonly Used Treatment Combinations
Treatment options commonly used for relapsed or refractory marginal zone lymphoma include:[2]
- R² – rituximab and lenalidomide (Rituxan and Revlimid)
- Rituximab (Rituxan) alone
- Zanubrutinib (BRUKINSA)
Targeted Therapies
The development of new anti-CD20 monoclonal antibodies, small molecule kinase inhibitors (drugs that block specific proteins involved in cancer cell growth), immunomodulators (substances that modify the immune response), and other therapeutic approaches has created new possibilities in treating relapsed or refractory marginal zone lymphoma.[1]
BTK Inhibitors
Several targeted therapy drugs may be used for relapsed or refractory disease, including:[8]
- Ibrutinib (Imbruvica)
- Zanubrutinib (Brukinsa)
- Lenalidomide (Revlimid)
Ibrutinib is a Bruton’s tyrosine kinase inhibitor, which means it blocks a specific protein that helps lymphoma cells grow and survive. This drug was approved by the U.S. Food and Drug Administration for treating relapsed or refractory marginal zone lymphoma. In a clinical trial, ibrutinib showed an overall response rate of 48 percent, with a complete response rate of 3 percent. The median time before the disease progressed was 14.2 months.[7]
Understanding how B-cell receptor signaling works in lymphoma development has identified this pathway as a reasonable target for treatment. Recent clinical research suggests that drugs targeting this pathway show significant promise for treating relapsed marginal zone lymphoma.[19]
