Vorinostat Plus Standard Immunoprophylaxis Cuts Risk of Graft-vs-Host Disease in Half
A new class of drugs reduced the risk of patients contracting a serious and often deadly side effect of bone marrow transplant treatments, according to a study by Choi et al published in The Lancet Oncology. The study, the first to test this treatment in humans, combined the drug vorinostat (Zolinza) with standard medications given after transplant, resulting in 22% of patients developing graft-vs-host disease compared to 42%of patients who typically develop this condition with standard medications alone.
“Graft-vs-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,” said first study author Sung Choi, MD, Assistant Professor of Pediatrics at the University of Michigan Medical School.
Vorinostat is currently approved by the FDA for the treatment of cutaneous T-cell lymphoma. Led by senior study author Pavan Reddy, MD, investigators at the University of Michigan found in laboratory studies that vorinostat had anti-inflammatory effects as well, which they hypothesized could be useful in preventing graft-vs-host disease.
Study Details
The study enrolled 61 older adults from the University of Michigan and Washington University in St. Louis who were undergoing a related-donor reduced-intensity conditioning hematopoietic stem cell transplant. Patients received a conditioning regimen of fludarabine and busulfan prior to infusion of peripheral blood stem cells. Graft-vs-host disease prophylaxis consisted of vorinostat in combination with standard immunoprophylaxis, tacrolimus and mycophenolate mofetil. Of the 61 participants, 50 completed the full 21-day course of vorinostat.
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.
Dual Effect
“This is an entirely new approach to preventing graft-vs-host disease,” Dr. Reddy said. Vorinostat targets histone deacetylases, which are different from the usual molecules targeted by traditional treatments.
“Vorinostat has a dual effect as an anticancer and an anti-inflammatory agent. That’s what’s potentially great about using it to prevent graft-vs-host [disease], because it may also help prevent the leukemia from returning,” said Dr. Reddy, who is also Co-Director of the Hematologic Malignancies and Bone Marrow Transplant Program at the U-M Comprehensive Cancer Center.
“We are encouraged by our findings,” Dr. Choi said. “Vorinostat combined with standard graft-vs-host disease prophylaxis after related-donor transplant appears to be safe and associated with lower than expected incidence of acute [graft-vs-host disease]. Future studies are needed to assess the effect of vorinostat in broader transplant settings. We are currently investigating vorinostat plus standard therapies to prevent [graft-vs-host disease] in transplants with an unrelated donor.”
Dr. Reddy is corresponding author of The Lancet Oncology article.
The study was funded by Merck, Leukemia and Lymphoma Society, the National Institutes of Health, St. Baldrick’s Foundation, and the Michigan Institute for Clinical and Health Research. The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
