OncoTargets and Therapy (Feb 2022)
Targeted Therapy for Relapsed/Refractory Follicular Lymphoma: Focus on Clinical Utility of Tazemetostat
Abstract
Ruben Raychaudhuri, Chaitra Ujjani Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USACorrespondence: Chaitra Ujjani, Tel +1 206-606-1955, Email [email protected]: The management of follicular lymphoma (FL) in the relapsed and refractory setting is challenging and an area of ongoing investigation. Epigenetic dysregulation has recently been shown to be a hallmark of FL. Mutations in histone-modifying genes are likely early, driver events in FL pathogenesis, and so are attractive targets to drug. Gain-of-function mutations in the histone methyltransferase EZH2 are common in FL and maintained through disease evolution. With mounting data supporting a critical role for EZH2 as an oncogenic driver for FL, the small molecule inhibitor, tazemetostat, was developed. Tazemetostat has shown promising activity in preclinical models and early phase trials. Importantly, responses were seen in patients with high-risk features. Based on these data, tazemetostat was approved in the US in 2020 for EZH2mut patients with FL who had received at least two prior lines of systemic therapy, or for EZH2wt patients without alternative treatment options. Here, we will review the biology of FL as it pertains to tazemetostat, the available clinical trial data, and future directions for this new therapy.Keywords: tazemetostat, follicular lymphoma, EZH2 mutation
