The administration of the histone deacetylase inhibitor vorinostat in patients undergoing matched related donor reduced-intensity conditioning allogeneic hematopoietic stem cell transplants could be an effective approach to reducing graft-versus-host disease (GVHD), according to the first-in-human clinical trial of 45 patients. The drug was added on days 10 to 100 to standard GVHD prophylaxis consisting of mycophenolate mofetil and tacrolimus.
After treatment, patients who received vorinostat had a significantly lower incidence of GVHD than their historical controls (22% vs 42%). They also had lower rates of grade 3 and 4 GVHD (4% vs 19%) as well as transplant-related mortality at 1 year (13% vs 19%). There were no significant differences in rates of infectious complications or incidence of relapse, indicating that vorinostat helped reduce the risk of GVHD in patients without further compromise.
Reference
Choi SW, DiPersio JF, Braun TM, et al. Targeting histone deacetylases as a new strategy for graft versus host disease prevention. Presented at: 54th American Society of Hematology Annual Meeting; December 8-11, 2012; Atlanta, GA. Abstract 740.
