Discovered nearly 45 years ago in the volcanic soils of fabled Easter Island in the Pacific, a drug first thought of as an antifungal agent has found a new purpose by boosting the survival of leukemia patients after blood stem cell transplants.
In a clinical trial conducted by Seattle Cancer Care Alliance’s partner organization, Fred Hutchinson Cancer Research Center, the addition of a third drug, sirolimus, to a standard two-drug regimen effectively cut in half the incidence of acute graft-vs.-host disease, or GVHD, a common and dangerous complication of these lifesaving procedures.
So convincing were the early results of the trial that the independent Data Safety and Monitoring Board, which advises such studies, halted it in July. The new combination using sirolimus saved lives, so it was considered unethical to withhold it any longer from the patients in the control arm of the trial who were taking only the standard two-drug therapy.
At the American Society of Hematology annual meeting in San Diego, SCCA’s Dr. Brenda Sandmaier on Sunday presented the interim study results that led to the decision, which in turn has already changed how patients at Seattle Cancer Care Alliance, and other participating hospitals are being treated.
“I do a lot of studies. It is not often you get to see an exciting result like this one,” said Sandmaier, who conducts research at Fred Hutch.
Ever since Fred Hutch scientists developed bone marrow transplants to cure blood cancers more than 40 years ago, GVHD has proven to be the most stubborn of side effects. In a transplant, the leukemia patient’s cancerous immune system — its army of infection-fighting white blood cells — is essentially swapped for that of a healthy donor. GVHD is caused when the donated immune cells (the graft) begin to attack the healthy tissues of the patient (the host). While years of careful adjustment have significantly trimmed the risk of GVHD, it still affects about half of leukemia patients who receive blood stem cells or marrow from a donor. The symptoms of rashes, blisters, liver damage and nausea are often temporary, but they can also become chronic, debilitating and deadly.
The key findings Sandmaier described from the trial were that patients taking the triple-drug combination containing sirolimus not only had a lower rate of acute GVHD, but scored substantially better on survival measures:
- Just 25 percent of those taking sirolimus as a third drug had moderate to severe GVHD, compared to 53 percent of those taking the two-drug combination.
- Rates of worrisome stage 3 or stage 4 GVHD fell fourfold, to 2 percent from 8 percent, in the triple-combo group.
- Deaths unrelated to leukemia relapse (and therefore most likely a result of GVHD) after one year fell to 5 percent from 15 percent.
- Overall survival one year after transplant rose to 85 percent from 72 percent in the sirolimus group.