Outcomes are gradually improving for patients who suffer from graft-versus-host disease (GVHD), one of the most serious complications of stem cell transplantation, and researchers are optimistic that further advances may be on the way.
“We have a half-dozen or so clinical trials evaluating newer agents at all levels of the disease,” says Corey Cutler, MD, MPH, a medical oncologist in the Dana-Farber/Brigham and Women’s Cancer Center Adult Stem Cell Transplantation Program who has a special interest in GVHD. “There is an evolving portfolio of a number of potential agents aimed at preventing or treating the disease.”
GVHD may develop following a stem cell or bone marrow transplant when the transplanted donor cells, recognizing the recipient’s tissues as foreign, mounts an immune attack on the recipient’s body. GVHD is less likely to occur if the donor’s cells are a close match to the recipient’s. Acute GVHD generally appears within 100 days of the transplant; chronic GVHD develops later and may be lifelong.
Drugs that suppress the immune system are frequently used to reduce GHVD symptoms, which can include gastrointestinal problems, dry or irritated eyes, skin rashes, fatigue and muscle weakness. “In general, we have better drugs than in the past, and our outcomes are better,” says Cutler. “And good supportive care makes a difference. With antiviral, antifungal and antibacterial therapy we are reducing the odds of serious infections because of the immune suppression.”
Among the drugs being evaluated in clinical trials at Dana-Farber is rituximab, a monoclonal antibody aimed at preventing chronic GVHD. Others, such as interleuken-2, may have potential to improve treatment of the initial manifestations of GVHD. The targeted drug ibrutinib is will be studied for benefit in more advanced stages of GHVD.
In one innovative trial, researchers are studying a drug called Tysabri that is currently used in multiple sclerosis treatment. In that disease, Tysabri targets molecular tags that cause immune cells to damage nerves in the brain. Cutler says those same tags direct immune cells to attack the intestinal tract in GVHD, which means Tysabri may be able to reduce gastrointestinal problems.
This intense clinical research activity in GVHD “is huge,” says Cutler. “We’re excited to finally have access to a whole bunch of new compounds for our patients.”
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