Systematic assessment of potential cardiac effects of the novel histone deacetylase (HDAC) inhibitor romidepsin

e19533 Background: Romidepsin is a novel pan-HDAC inhibitor with single-agent activity in T-cell lymphoma. HDAC inhibitors reportedly have cardiovascular effects, in particular, QTc prolongation. To systematically and rigorously evaluate the potential cardiac effects of romidepsin, a cardiac safety monitoring plan was developed after discussions with the FDA. Methods: The effect of romidepsin on the change from baseline QTcF (Fridericia's correction) at key pharmacokinetic and pharmacodynamic (PD) time points was investigated. ECGs from 110 pts with advanced malignancies in 3 open-label, clinical studies of romidepsin 14 mg/m2 administered on days 1, 8 and 15 of a 28 day cycle were evaluated by blinded, independent assessors. Results: A mean 2.7 msec increase (90% confidence interval [CI]: 0.2, 5.3) in QTcF interval from a baseline post-antiemetic administration to after infusion of romidepsin was measured. A subanalysis of 74 patients (pts) evaluated QTcF from pre-antiemetic to post-romidepsin showed a m...