Sung W. Choi, MD, Assistant Professor, University of Michigan, discusses the results of a phase I/II trial examining the use of the histone deacetylase (HDAC) inhibitor vorinostat in graft-versus-host disease (GVHD) prevention.

Bone marrow transplantation is a potentially curative therapy for many hematological cancers as well as non-malignant conditions. GVHD remains a barrier to successful transplantation, Choi says, yet prevention therapies have not made much progress in the past 20 to 30 years.

The trial used a standard conditioning background of fludarabine and busulfan along with standard GVHD prophylaxis (tacrolimus and mycophenolate mofetil) then added the investigational agent, vorinostat. The combination was taken for 111 days before, during, and after bone marrow transplant.

The primary endpoint was the cumulative incidence of grade 2-4 acute GVHD with a target risk of 25% by day 100. The endpoint was reached: the cumulative incidence of day 100 grade 2-4 acute GVHD was 21% in the study group compared to 48% in the control, according to Choi. Further, transplant-related mortality was reduced and overall survival saw improvement in the study arm.