A framework to challenge the dogma of incurability in follicular lymphoma

Follicular lymphoma (FL) has traditionally been considered an incurable malignancy characterized by repeated relapses. However, emerging long-term data are increasingly challenging this paradigm. With rituximab, median overall survival approaches 20 years, and only 35-40% of patients require more than one treatment line. Drawing on frameworks established in chronic viral infections and other hematologic malignancies, including chronic myeloid leukemia and multiple myeloma, this review examines the evolving concepts of cure and functional cure. We propose a framework supporting the probability of functional cure based on several observations: durable remission following treatment discontinuation; absence of clinically meaningful progression, sustained deep remission defined by sensitive biomarkers including minimal residual disease and PET/CT; and normalization of survival relative to the general population and patient-reported quality of life. We further discuss how early clinical milestones, such as event-free survival at 24 months (EFS24) and complete remission at 30 months (CR30), may also assist in identifying patients with particularly favorable long-term disease trajectories. Together, these findings support reconsideration of long-standing assumptions regarding the natural history of FL and provide a conceptual framework for defining functional cure in FL, with implications for therapeutic goals, survivor follow-up strategies, biomarker development, and personalized therapeutic.