HIV drug reduces GVHD in bone marrow transplant patients
Repurposing the HIV drug maraviroc dramatically reduced the risk of graft-versus-host disease in bone marrow patients, according to results of a phase ½ single-group trial.
GVHD, a leading cause of death associated with bone marrow transplants, occurs when newly transplanted immune cells attack healthy tissue. Up to 50% of patients who receive transplants from related donors and up to 70% of patients who receive transplants from unrelated donors develop GVHD, according to background information in the study.
Maraviroc (Selzentry, ViiV Healthcare), an inhibitor of T-cell chemotaxis, blocks the CCR5 receptor on lymphocytes by redirecting immune cells away from sensitive organs such as the liver, according to researchers.
In this study, Ran Reshef, MD, assistant professor in the division of hematology-oncology in the Abramson Cancer Center at the Hospital of the University of Pennsylvania, and colleagues evaluated 38 patients with high-risk blood cancers who underwent hematopoietic stem-cell transplantation.
All patients received standard GVHD prophylaxis with oral tacrolimus and IV methotrexate. They also received maraviroc twice daily for 33 days, beginning 2 days prior to treatment and continuing until 30 days post-transplant.
At 100 days after transplant, none of the patients developed GVHD in the liver or gut, the researchers said.
By 6 months post-transplant, 5.9% of patients overall had developed severe GVHD — defined as grade-3 or grade-4 — in either the liver or gut. Prior studies have shown 21.9% of similar patients who receive standard prophylaxis but do not receive maraviroc develop severe GVHD within 6 months of transplant, the researchers wrote.
One year after transplant, 14.7% of patients treated with maraviroc developed severe GVHD. Prior studies have shown 29.4% of patients who receive standard prophylaxis but do not receive maraviroc develop severe GVHD within 1 year of transplant, according to researchers.
Maraviroc did not increase toxicity or affect the rate of relapse, the researchers said.
“This is a novel way for us to try to decrease treatment-related complications among bone marrow transplant patients without also reducing their new immune system’s ability to attack their cancer,” Reshef said in a press release. “Just like in real estate, immune responses are all about location, location, location … We’re using maraviroc, which was initially designed to prevent certain types of HIV from entering healthy cells in the body, as a traffic signal to direct the donor’s immune cells away from those places in the body where they might cause GVHD.”
Reshef and colleagues plan to study whether a longer treatment regimen of maraviroc will extend the protective effect in patients who undergo hematopoietic stem-cell transplantation.