The study, the first to test this treatment in humans, shows promise to prevent graft-versus-host disease. It combined the drug vorinostat with standard medications given after transplant, resulting in 21 percent of patients developing the condition compared to 42 percent of patients who typically develop it with standard medications alone.
"Graft-versus-host disease is the most serious complication from transplant that limits our ability to offer it more broadly. Current prevention strategies have remained mostly unchanged over the past 20 years. This study has us cautiously excited that there may be a potential new way to prevent this condition," says Sung Choi.
Vorinostat is currently approved by the United States Food and Drug Administration to treat certain types of cancer. But researchers, led by Pavan Reddy, found in laboratory studies that the drug had anti-inflammatory effects as well – which they hypothesized could be useful in preventing graft-versus-host disease, a condition in which the new donor cells begin attacking other cells in the patient's body.
Participants were older adults who were undergoing a reduced-intensity bone marrow transplant with cells donated from a relative. Patients received standard medication used after a transplant to prevent graft-versus-host disease. They also received vorinostat, which is given as a pill taken orally. The researchers found vorinostat was safe and tolerable to give to this vulnerable population, with manageable side effects. In addition, rates of patient death and cancer relapse among the study participants were similar to historical averages.
The results mirror those found in the laboratory using mice. Reddy has been studying this approach in the lab for eight years. "This is an entirely new approach to preventing graft-versus-host disease," Choi says. Specifically, vorinostat targets histone deacetylases, which are different from the usual molecules targeted by traditional treatments. "Vorinostat has a dual effect as an anti-cancer and an anti-inflammatory agent. That is what is potentially great about using it to prevent graft-versus-host, because it may also help prevent the leukemia from returning," Choi says.
The study is continuing to enroll participants. The researchers hope next to test vorinostat in patients receiving a transplant from an unrelated donor, which carries an even greater risk of graft-versus-host disease.
MEDICA.de; Source: University of Michigan