An experimental drug combination for preventing graft-versus-host disease (GVHD) was not significantly better than the standard regimen on key end points. Combining tacrolimus and sirolimus, both immunosuppressive compounds, did not provide a statistically significant, GVHD-free survival benefit over the long-used standard of care, which is tacrolimus plus methotrexate.

The tacrolimus/sirolimus treatment did have some upsides that could prove advantageous for certain patients. Advantages included that patients engrafted slightly more rapidly and suffered much less from mucositis. However, downsides included an increased risk of veno-occlusive disease and a slight increase in the incidence of late-onset GVHD.

“We were a little disappointed in the results, but excited to offer an alternative to the standard of care for the past 25 years,” said first author Corey Cutler, MD, MPH, of the Dana-Farber Cancer Institute in Boston, Massachusetts. Cutler has worked with colleagues since 2000, leading clinical studies of sirolimus in hopes that it would improve survival from GVHD than the standard treatment.

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This phase III randomized, controlled trial was carried out by the Bone and Marrow Clinical Trials Network (BMT CTN) at 26 centers. It enrolled more than 300 patients, most of whom had acute leukemia in remission. The patients then received stem cell transplants from a matched sibling donor.

The primary end point of 114-day acute GVHD-free survival was 67% in the tacrolimus/sirolimus group and 62% in the tacrolimus/methotrexate group, which was not a statistically significant difference. At 2 years after transplantation, no difference existed in disease-free survival and overall survival rates.

“This study establishes this regimen as an alternative to the standard of care—it could be preferable in certain scenarios,” Cutler said. “It will continue to be the standard of care at Dana-Farber.”

This study was presented at the American Society of Hematology annual meeting, held in Atlanta, Georgia, December 8-11, 2012.