First-Line Treatment for FL

Choosing a first-line treatment for FL is based on clinical and laboratory features identified as having prognostic significance, as well as patient comorbidities and toxicity of treatment. The approach may be watchful waiting for asymptomatic patients with low tumor burden or aggressive antibody-chemoinduction therapy followed by maintenance. With many patients living longer, first-line treatments need to minimize toxicity.

Stage I-II Disease

Standard treatment has been local radiotherapy, leading to long-term disease control in about 70% of patients. Recently, more patients are being considered for chemotherapy, immunotherapy, and rituximab monotherapy with or without radiotherapy. Studies have shown improved PFS but not OS with this approach.

Advanced Stage, Low Tumor Burden, Indolent Course

For some patients an initial watch-and-wait approach may be feasible, waiting until clinically significant disease progression. Rituximab monotherapy may be an option for patients with asymptomatic, advanced-stage, low-tumor-burden FL. Although no major OS differences have been seen with rituximab vs watch and wait, patients taking rituximab maintenance therapy may have a longer time without the need for treatment or retreatment. 

Advanced Stage, High Tumor Burden, Active Disease 

Chemoimmunotherapy is currently the standard treatment for patients with active disease and high tumor burden, and the addition of rituximab to chemotherapy improved the overall patient response rate, duration of response, OS, and PFS. Standard treatment options for patients who require active therapy include rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP); and fludarabine-containing treatments.

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R-bendamustine is also an effective treatment with lower initial toxicity. Rituximab plus lenalidomide (R-L) has been studied as a chemotherapy-free immunomodulatory treatment and has had similar outcomes to rituximab plus chemotherapy.

Obinutuzumab, a fully humanized anti-CD20 monoclonal antibody, with enhanced antibody dependent cellular cytotoxicity, in association with bendamustine, CHOP, or CVP chemotherapy showed improvement in 3-year PFS, but was associated with more serious adverse events. Obinutuzumab may be an alternative to rituximab for patients with high-risk FLIPI.