Hypomethylating Agents in Lymphoma

Epigenetic mutations are frequent and pathogenic in select subtypes of lymphoma, and agents modulating DNA and histone methylation—such as inhibitors of DNMT and EZH2, respectively—have demonstrated promise in treating these diseases. In particular, lymphomas derived from the germinal center—GC-DLBCL, FL, and AITL—are all characterized by epigenetic derangements. In an effort to target these derangements, DNMT inhibitors have been investigated as a means of improving responsiveness to chemotherapy in DLBCL patients, or as monotherapy or in combination with other epigenetic agents in the treatment of TCL. Histone methyltransferase inhibitors have demonstrated effectiveness in R/R FL patients with EZH2-activating mutations. New treatment options that target the pathogenesis of disease are needed. HDAC inhibitors have been in the clinic for over a decade for the treatment of lymphoma, and now methyltransferase inhibitors are finding their niche for this disease.