Highlights
- Follicular lymphoma is the second most common form of non-Hodgkin lymphoma worldwide.
- Advanced therapies and ongoing research offer hope for improved outcomes in FL treatment.
Summary and Overview
Follicular lymphoma (FL) is a slow-growing B-cell non-Hodgkin lymphoma, accounting for about 5% of hematologic cancers worldwide. It primarily affects older adults, especially those of Ashkenazi Jewish descent and Whites, and often presents as painless, persistent lymphadenopathy. Diagnosis involves lymph node biopsy, immunohistochemical markers, and detection of the t(14;18) translocation causing BCL2 overexpression. Staging and risk stratification, including the Follicular Lymphoma International Prognostic Index (FLIPI), guide prognosis and treatment.
Treatment varies from active surveillance in asymptomatic, low tumor burden cases to chemoimmunotherapy and targeted therapies for advanced or symptomatic disease. New options include anti-CD20 antibodies, Bruton’s tyrosine kinase inhibitors, bispecific antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, especially for relapsed or refractory FL. Despite advances, FL remains incurable with frequent relapses and transformation risk, requiring ongoing monitoring and individualized care.
Signs, Diagnosis, and Staging
FL often grows slowly with many patients asymptomatic at diagnosis. Common signs include painless swollen lymph nodes and occasional systemic “B symptoms” such as night sweats, fever, and weight loss. Bone marrow involvement may cause blood abnormalities and increased infection risk.
Diagnosis relies on lymph node biopsy with histology and immunohistochemistry confirming B-cell markers and genetic tests identifying the t(14;18) translocation. Imaging with PET-CT or CT scans assesses disease extent, while bone marrow biopsy evaluates marrow involvement. Elevated lactate dehydrogenase (LDH) may indicate higher disease burden or transformation.
Staging follows the Ann Arbor system, from Stage I (localized) to Stage IV (disseminated, including bone marrow). Genetic features such as BCL2 overexpression further characterize the disease and inform treatment decisions.
Pathophysiology
FL arises from germinal center B-cells with a characteristic t(14;18) translocation leading to BCL2 overexpression, which inhibits apoptosis and allows malignant cell survival. Less commonly, mutations in BCL6 contribute to pathogenesis. FL can transform into aggressive lymphomas like diffuse large B-cell lymphoma, often signaled by clinical changes and elevated LDH.
Treatment Approaches
Management depends on disease stage, symptoms, and patient factors. Active surveillance is appropriate for asymptomatic patients with low tumor burden. When treatment is needed, frontline therapy typically involves chemoimmunotherapy combining anti-CD20 antibodies (rituximab or obinutuzumab) with chemotherapy. Radiation may be used in early-stage disease.
Maintenance rituximab after induction prolongs remission but requires balancing infection risks. Relapsed or refractory FL may be treated with repeated regimens, novel agents like PI3K inhibitors, lenalidomide plus rituximab, BTK inhibitors, or advanced therapies such as CAR-T and bispecific antibodies (e.g., mosunetuzumab), which offer promising efficacy with manageable side effects.
Emerging therapies targeting molecular pathways and apoptosis regulators are under investigation to improve outcomes further.
Side Effects and Prognosis
Fatigue is a common and persistent symptom from disease and treatment effects, impacting quality of life. Immunochemotherapy and monoclonal antibody treatments can cause side effects, including increased infection risk.
FL generally has a favorable prognosis with about 90% five-year survival; however, many patients present at advanced stages. Risk stratification with FLIPI predicts outcomes, with higher risk linked to poorer survival. Approximately 30–40% of patients may experience transformation to aggressive lymphoma, worsening prognosis.
Living with Follicular Lymphoma
Many patients live with FL as a chronic, indolent disease, often monitored without immediate treatment. For those treated, maintenance therapies and novel treatments improve disease control. Managing side effects and relapses, alongside psychosocial support and patient education, are essential components of care. Resources such as peer support and expert guidance help patients maintain quality of life.
Research and Future Directions
Recent advances include CAR-T therapies and bispecific antibodies offering durable responses in relapsed FL. Mosunetuzumab presents a convenient off-the-shelf immunotherapy with fewer side effects than CAR-T. Immunochemotherapy combined with targeted agents remains central, while BTK inhibitors and antibody-drug conjugates are under study. Trials like CELESTIMO are evaluating novel combinations to optimize treatment.
For transformed FL, treatment resembles aggressive lymphoma protocols, though standardized approaches are lacking. Ongoing research focuses on personalized therapies, molecular predictors of response, and overcoming resistance to improve long-term outcomes in this challenging disease.
The content is provided by Avery Redwood, Scopewires
