Vorinostat

• Prolongation of prothrombin time and INR with simultaneous administration of coumarins.
• Severe thrombocytopenia and gastrointestinal haemorrhage when administered simultaneously with other histone deacetylase inhibitors (e.g. valproic acid).

Recent studies have evaluated the humanized CCR4 monoclonal antibody, mogamulizumab, in relapsed/refractory MF and SS, showing a significant benefit in progression-free survival (PFS). In August 2018, mogamulizumab was approved by the FDA for the treatment of patients with relapsed/refractory MF/SS who have failed at least one treatment. The approval was based on the Phase III MAVORIC trial, which compared mogamulizumab to vorinostat, an FDA-approved drug for this indication, in 372 patients. In this study, mogamulizumab was found to have superior PFS with a median of 7.7 months compared to 3.1 months in the vorinostat group, with a hazard ratio of 0.53, p<0.001 (Kim YH et al. 2018).

1. Grant S et al (2007) Vorinostat. Nat Rev Drug Discov 6: 21-22

2. Kim YH et al. (2018) Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol19:1192-1204.