This article is more than 5 years old. Information may no longer be current.
Sirolimus failed to reduce GVHD rates after HSCT
Click Here to Manage Email Alerts
The incidence of graft-versus-host disease after related donor allogeneic hematopoietic stem cell transplantation was similar among patients who received tacrolimus with sirolimus or methotrexate, according to phase 3 study results.
However, the sirolimus combination was associated with more rapid engraftment and less oropharyngeal mucositis, results showed.
Corey Cutler
Corey Cutler, MD, MPH, FRCPC, associate professor of medicine at Harvard Medical School and senior physician in the department of medical oncology at Dana-Farber Cancer Institute, and colleagues randomly assigned 151 patients (median age, 45 years) to tacrolimus plus sirolimus (Rapamune, Pfizer). The other 153 patients (median age, 43 years) received tacrolimus plus methotrexate.
The most common primary malignancies among patients in both arms were acute myeloid leukemia (sirolimus, 47%; methotrexate, 41%) and acute lymphoblastic leukemia (sirolimus, 34%; methotrexate, 44%). Disease status at transplantation was comparable between arms.
The probability of grade 2 to grade 4 acute GVHD-free survival at day 114 was similar between patients who received sirolimus or methotrexate (67% vs. 62%; P=.38). The incidence of grade 2 to grade 4 GVHD also was comparable between arms (26% vs. 34%; P=.48).
Patients assigned sirolimus demonstrated a trend toward increased incidence of chronic GVHD at 2 years (53% vs. 45%; P=.06); however, results of a multivariate analysis indicated the risk for chronic GVHD was comparable between arms (HR=1.27; 95% CI, 0.91-1.76).
Researchers reported a significantly shorter median time to neutrophil engraftment among patients who received sirolimus (14 days vs. 16 days; P˂.001). Median time to platelet engraftment also was shorter in the sirolimus arm (16 days vs. 19 days; P=.03).
Treatment-related toxicity was comparable between the arms with the exception of oropharyngeal mucositis, which was less severe in the sirolimus arm (Oral Mucositis Assessment Scale peak score, 0.70 vs. 0.96; P˂.001).
Researchers reported similar rates of 2-year RFS (53% vs. 54%; P=.77) and 2-year OS (59% vs. 63%; P=.36) among the sirolimus and methotrexate arms.
“As an alternative to tacrolimus and methotrexate, the tacrolimus and sirolimus regimen can be considered in patients undergoing TBI-based transplantation who are at a higher risk of oropharyngeal mucositis … and in patients in whom timely engraftment is required (due to ongoing infection or risk of infection) after appropriate screening for risks of excessive hepatotoxicity are excluded,” Cutler and colleagues wrote. “Further studies to test novel GVHD prophylaxis regimens with a goal of improving HCT outcomes are required.”
Disclosure: The study was funded in part by the National Heart, Lung and Blood Institute and the NCI. The researchers report no relevant financial disclosures.
Click Here to Manage Email Alerts