Upfront identification of high-risk follicular lymphoma

Follicular lymphoma (FL) is a common disease with clinically indolent behavior, and a long natural history for the majority of patients. Despite excellent therapeutic strategies currently available for FL, approximately 10%-20% of patients will experience early disease progression, defined as occurring within two years of diagnosis. These patients have poor outcomes, with overall survival at 5 years ranging between 37% and 50%. Much of the biology driving early progression and inferior survival is attributed to early transformation events; however, transformation alone does not account for all the observed clinical heterogeneity and survival differences among patients. Several clinical, genetic, and molecular alterations in FL have been discovered that help define subsets of patients at risk for multiply relapses and refractory disease, and are slowly making their way into risk calculators to be used in daily practice. Additionally, the role of functional imaging with PET scan, as well as circulating and cell free tumor DNA are being evaluated as tools to define high-risk subsets of patients with FL. This review seeks to provide an over view of current and evolving biomarkers that define high-risk FL at diagnosis. The goal is for these tools to assist clinicians in integrating these rapidly evolving prognosis models into clinical practice, in the hopes of risk-stratifying treatments and improving outcomes for patients.