Study Sets New Standard for Graft-Versus-Host Disease Prevention After Stem Cell Transplant

Clinicians have a new standard for graft-versus-host disease (GVHD) prevention after allogeneic hematopoietic stem cell transplantation, according to results from a phase III study published June 22 in the New England Journal of Medicine. 

The new standard is more effective at preventing GVHD and came with less side effects, compared with the current gold standard.

In an allogeneic bone marrow transplant, the healthy stem cells come from the bone marrow of a relative who is not an identical twin of the patient or from an unrelated donor who is genetically similar to the patient. But a bone marrow transplant can cause GVHD, a serious and life-threatening complication. 

As opposed to an organ transplant where the patient’s immune system will attempt to reject only the transplanted organ, in GVHD the new or transplanted immune system can attack the entire patient and all organs.

The current gold standard to prevent GVHD after bone marrow transplants is a combination of two drugs: a calcineurin inhibitor, such as tacrolimus or cyclosporine, and methotrexate. 

In the current phase III study, researchers from multiple institutions tested this standard to prevent GVHD against an experimental regimen of three drugs: cyclophosphamide, tacrolimus, and mycophenolate mofetil. 

“More than half patients in the cyclophosphamide platform were alive, free of grade III-IV acute GVHD and chronic GVHD needing immunosuppression, and without disease relapse or progression versus a third in the methotrexate and tacrolimus arm,” says Bolaños-Meade. “There were also a series of secondary endpoints showing less severe acute GVHD, and less chronic GVHD. Very importantly this was seen without an increase on relapses as historically — the better control of GVHD, the more cancer relapses. In this case we have better control of GVHD, but no more relapses.”

The researchers say that for the first time since the 1980s, we have a more effective drug therapy to prevent severe cases of GVHD, and therefore, we have a new standard of care. 

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Sources:

Javier Bolaños-Meade, Mehdi Hamadani, Juan Wu, Monzr M. Al Malki, Michael J. Martens, Lyndsey Runaas, Hany Elmariah, Andrew R. Rezvani, Mahasweta Gooptu, Karilyn T. Larkin, Brian C. Shaffer, Najla El Jurdi, Alison W. Loren, Melhem Solh, Aric C. Hall, Amin M. Alousi, Omer H. Jamy, Miguel-Angel Perales, Janny M. Yao, Kristy Applegate, Ami S. Bhatt, Leslie S. Kean, Yvonne A. Efebera, Ran Reshef, William Clark, Nancy L. DiFronzo, Eric Leifer, Mary M. Horowitz, Richard J. Jones, Shernan G. Holtan. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. New England Journal of Medicine, 2023; 388 (25): 2338 DOI: 10.1056/NEJMoa2215943

Johns Hopkins Medicine. (2023, June 22). Study sets new standard for graft-versus-host disease prevention after stem cell transplant. ScienceDaily. Retrieved June 28, 2023 from www.sciencedaily.com/releases/2023/06/230622142348.htm

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