New Combo Slows Graft Versus Host Disease During Blood Cancer Treatment

Cancer patient talking to doctor while lying in bed
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A new study suggests that a novel regimen of immune-suppressing drugs comprising, cyclophosphamide, abatacept, and tacrolimus, is a better option for graft versus host disease (GvHD) in people being treated for blood cancer.

The studies were led by researchers at NYU Langone Health and its Laura and Isaac Perlmutter Cancer Center. They presented their results at the American Society of Hematology’s annual meeting in Atlanta.

“Our preliminary results show that using abatacept in combination with other immune-suppressing drugs is both safe and an effective means of preventing GvHD after stem cell transplantation for blood cancers,” says study lead investigator and hematologist Samer Al-Homsi. “Signs of GvHD with abatacept were minimal and mostly treatable. None were life-threatening,” adds Al-Homsi, a clinical professor in the Department of Medicine at NYU Grossman School of Medicine and Perlmutter Cancer Center.

Stem cell transplantation, especially from members of the same family, has transformed the treatment of leukemia, a disease that afflicts nearly a half-million Americans. And although the treatment is successful for many, half of those who undergo the procedure experience some form of GvHD, when the newly implanted immune cells recognize their host’s body as “foreign” and then target it for assault.

Most cases of GvHD are treatable, but an estimated one in 10 can be life-threatening. Immune-suppressing drugs are used to prevent GvHD by the donated cells, and patients, who are mostly unrelated, are matched whenever possible with donors beforehand to make sure their immune systems are as similar as possible.

The investigation showed that among the first 23 adult patients with aggressive blood cancers given the post-transplant drug regimen over a period of three months, just four showed early signs of GvHD, including skin rash, nausea, vomiting, and diarrhea. Another two developed reactions weeks later, mostly skin rashes. All were successfully treated with other medications for their symptoms. None developed more severe symptoms, including liver damage or difficulty breathing.

However, one patient, whose transplant failed, died of recurring leukemia. The rest (22 men and women, or 95 percent) remain cancer free more than five months after their transplant, with donated cells showing signs of producing new, healthy, and cancer-free blood cells.

The current study involved stem cell transplantation from closely related (half-matched) donors and patients, including parents, children, and siblings, but whose genetic make-up was not identical, with the drug combination increasing the likelihood of successful transplantation.

“By improving the odds against developing graft-versus-host disease, we can expand the pool of family members who can safely serve as stem cell transplant donors for people with blood cancers, regardless of their ethnic background,” says Al-Homsi.

The new regimen replaces the traditionally used drug mycophenolate mofetil with abatacept. Al-Homsi says abatacept is “more targeted” than mycophenolate mofetil and prevents immune T cells from becoming “activated,” a necessary step before these immune cells can attack other cells.

Also, as part of the revised treatment, researchers were able to shorten the treatment time for tacrolimus to three months, from the original treatment window of six to nine months. This is important since the drug has potential toxic side effects on the kidney.

“Alternative drug regimens are urgently needed to prevent GvHD, especially among those for whom finding a close match is challenging,” says senior study investigator and hematologist Maher Abdul Hay, MD, an assistant professor at NYU Grossman School of Medicine and Perlmutter Cancer Center and director of its clinical leukemia program.

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