Anticancer agent reduces complications after stem-cell transplant
Vorinostat, a drug already approved by the FDA for the treatment of cutaneous T-cell lymphoma, has been found to reduce the risk of graft-versus-host disease (GVHD) in persons undergoing allogeneic hematopoietic stem-cell transplantation. In GVHD, donor cells attack the patient's own cells.
“[GVHD] is the most serious complication from transplant that limits our ability to offer it more broadly,” explained lead study author Sung W. Choi, MD, of the University of Michigan (UM) Comprehensive Cancer Center in Ann Arbor, in a statement from the UM Health System. “This study has us cautiously excited that there may be a potential new way to prevent this condition.”
UM researchers found that vorinostat, a histone deacetylase inhibitor, also has anti-inflammatory properties, which could be useful in combating GVHD. After conducting studies in mice, Choi's team enrolled 45 adults (median age 58 years) in a phase 1/2 trial that combined vorinostat with a standard GVHD prophylaxis regimen of tacrolimus and mycophenolate mofetil. Participants were undergoing a reduced-intensity bone-marrow transplant with cells donated from a relative.
At day 100, grade 2-4 acute GVHD was significantly lower among the 45 patients given vorinostat than among control patients receiving standard treatment (22% vs 42%). Severe grade 3-4 acute GVHD at day 100 was also reduced among vorinostat users (4% for vorinostat recipients vs 19% for controls), as was transplant-related mortality at 1 year (13% for vorinostat recipients vs 19% for controls).
“The incidence of [acute] GVHD was globally diminished in all target organs, and all but one patient responded rapidly to standard steroid therapy,” wrote the investigators in an abstract presented at the American Society of Hematology annual meeting held in Atlanta, Georgia, December 8-11, 2012.
The incidence of relapse was similar between the study group and the controls (17% vs 20%, respectively), and no difference was seen in the rate of infectious complications.