Treatment of Refractory/Relapsed FL

Many patients remain in remission for years after initial treatment, particularly with rituximab maintenance therapy in appropriate cases. However, the disease carries a high risk of relapse, which is not easy to identify early on.

When choosing a treatment for relapsed disease, clinicians should consider the same parameters for first-line therapy, initial treatment tolerance, and duration of response. The standard of care is to administer chemoimmunotherapy followed by maintenance rituximab. Another treatment possibility for these patients is high-dose chemotherapy with autologous stem cell support. Anti-CD20 monoclonal antibody with bendamustine or lenalidomide has shown some of the best results in recent trials, particularly for patients who have not responded well to rituximab.

Novel agents currently under study may also be effective for relapsed patients. These agents include drugs harnessing the immune system, such as PD-1 pathway inhibitors, anti-CD47 with rituximab, bispecific antibodies that activate cytotoxic T cells and bind to malignant cells, and anti-CD19 chimeric antigen receptor T-cell therapy.

Drugs targeting epigenetic modification are also under study. About 25% of cases have a mutation in the epigenetic modifier EZH2. The oral inhibitor tazemetostat targets EZH2 and is currently in a phase 2 trial with promising results for overall response rate. 

Continue Reading

Future Directions for FL

With rapid advances in staging, diagnosis, and treatment, FL is a potentially curable disease with long-term survival possible, even with advanced-stage disease. Future advances need to elucidate patients most at risk of relapse or early progression.

The authors noted that the current treatment strategies take a “one size fits all approach.” Improving outcomes will require a personalized approach to identify factors that can predict progression or relapse and provide more personalized initial treatment. 

“In the future, a personalized evaluation of the patient’s specific clinical, genetic, and epigenetic factors may help determine the most appropriate treatment for each patient,” concluded the investigators.

Disclosure: Some of the authors disclosed financial relationships with pharmaceutical companies and medical device manufacturers. For a full list of disclosures, please refer to the original study.


Luminari S, Trotman J, Massimo F. Advances in treatment of follicular lymphoma. Cancer J. 2020;26(3):231-240.