One Size Does Not Fit All: Who Benefits From Maintenance After Frontline Therapy for Follicular Lymphoma?

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma and the most common indolent B-cell malignancy. The disease often presents in advanced stage and can often be observed before initiation of therapy. Although the incidence is only approximately 15,000 new cases per year, the prevalence is substantially higher owing to the favorable overall survival (OS) of most patients. The most impactful advance responsible for the improvement of OS in FL was the introduction of the anti-CD20 monoclonal antibody (mAb) rituximab over 20 years ago. Phase III trials demonstrate that rituximab improves the OS in FL when combined with chemotherapy. However, unlike aggressive B-cell lymphomas, advanced stage FL is generally incurable and often displays a pattern of progressively shorter remissions with subsequent lines of therapy. Hence, maintenance strategies have been developed to prolong remissions achieved with frontline therapy. The value of maintenance after frontline therapy has been most extensively studied with extended treatment of anti-CD20 mAb, but recent approaches include chemotherapy-free combinations and targeted therapies given for extended durations. Here, we review relevant data that provide rationale in support of maintenance therapy in FL as well as the risks and limitations of a "one-size-fits-all" approach. Importantly, we note the biologic and clinical heterogeneity across patients with FL that must be considered when making clinical decisions. Finally, we highlight ongoing research that explores response-adapted approaches based on the depth of response as defined by PET scans and assays for minimal residual disease (MRD) that aim to better personalize individual management strategies.