Bortezomib drug effective against chronic GVHD

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Researchers at UC Davis have found that the drug bortezomib effectively treats chronic graft-versus-host disease (GVHD), a common and debilitating side effect from allogeneic hematopoietic stem cell transplants. The trial showed that bortezomib provides better outcomes than existing treatments and does not impair the immune response against residual cancer cells, or the graft-versus-tumor effect (GVT).

"Bortezomib helped a group of patients who desperately needed a treatment, having failed multiple different therapies," said UC Davis hematologist and associate professor Mehrdad Abedi, lead author on the paper. "The drug fights chronic graft-versus host disease, and unlike other GVHD therapies such as steroid, cyclosporine or mycophenolate, it treats chronic GVHD without dampening the graft-versus-tumor effect, which can be critically important to help patients avoid relapse. In fact, because bortezomib is an anti-cancer drug, it potentially attacks cancer cells in its own right."

The trial results were published in October in the journal Blood.

Chronic GVHD strikes patients who have received stem cell transplants from donors, commonly called allogeneic transplants. Although the transplants are close matches, they are not identical, and donor cells can attack the recipient, damaging skin, lungs, kidneys and other organs, which can be life threatening.

Developed by Millennium Pharmaceuticals, bortezomib has been used to treat multiple myeloma, leukemia and lymphoma. The drug also has been studied against acute GVHD, making it a promising option against the chronic version of the disease.

The researchers first studied bortezomib in mice, in which the drug delivered excellent results.

The investigation, in collaboration with William Murphy, professor and acting chair of the Department of Dermatology and a co-senior author, found that bortezomib suppresses the donor immune cells that cause GVHD.

"We then tested this concept in patients with chronic GVHD in collaboration with members of our bone marrow transplant team, hematologist-oncologists Carol Richman and Joseph Tuscano," Abedi said. "Almost all the patients who tolerated and remained on the treatment responded. In some cases, individual responses were quite dramatic. We were able to stop their other immunosuppressive medications and keep the patients under control with just weekly injections of bortezomib."

Abedi added that one patient had severe hemolytic anemia that did not respond to several lines of therapy.

"After receiving bortezomib, the patient's symptoms improved, and we were able to take her completely off steroid and other immunosuppressive medications," he said. "Another person had multiple ulcers, which completely healed. These were patients who had been on all different kinds of medications and had no response."

Research is continuing on bortezomib against chronic GVHD. Abedi and colleagues are now looking at a potential oral version of the drug and a similar agent, which would alleviate the need for weekly injections and could have fewer side effects.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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