romidepsin + lenalidomide

A combination regimen of the histone deacetylase inhibitor romidepsin and the immunomodulatory agent lenalidomide investigated as a chemotherapy-free biologic therapy for peripheral T-cell lymphomas and other lymphomas. Romidepsin inhibits class I histone deacetylases leading to increased histone acetylation, altered gene expression, and apoptosis; lenalidomide modulates the immune microenvironment via cereblon-dependent degradation of transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), enhances T-cell and NK-cell function, and has direct antineoplastic effects. Preclinical models in T-cell lymphoma demonstrated synergistic or additive cytotoxicity with increased apoptosis, ROS generation, ER stress/UPR activation, and inhibition of AKT, MAPK/ERK, and STAT3 signaling when combined. Clinically, phase I/II and multicenter phase II studies have evaluated this doublet in relapsed/refractory lymphomas and as initial therapy for previously untreated peripheral T-cell lymphoma patients ineligible for intensive chemotherapy, showing feasibility, expected hematologic toxicities, and encouraging response rates and durations, particularly in angioimmunoblastic T-cell lymphoma subtypes.[1][5][2][4][6]

Other names

romidepsin and lenalidomide