FDA Approves First-Ever Treatment to Prevent Graft Vs. Host Disease

Muna Qayed, MD, MsCR, Benjamin K. Watkins, MD, and Amelia Langston, MD

Photo: Javier De Jesus

The team at Winship Cancer Institute of Emory University soon diagnosed Redd with myelodysplastic syndrome, a type of cancer in which a patient’s bone marrow no longer produces normal amounts of healthy blood cells.

That’s how Redd ended up in the office of Amelia Langston, MD, director of Winship’s Bone Marrow and Stem Cell Transplant Program and medical director of Winship’s Cancer Network, Winship 5K Research Professor and executive vice chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine. A bone marrow transplant specialist, Langston treats patients with leukemia, myelodysplastic syndrome and other blood cancers.

“I looked over all your records,” Redd recalls Langston as saying to him at their first meeting. She explained why a stem cell transplant was his best treatment option. He added, “She looked me square in the face, and she said, ‘I want you to understand one thing: I might kill you.’”

Eight years later, Redd is still very much alive, thanks to a successful transplant that included enrollment in a clinical trial for abatacept, a drug Emory researchers hypothesized would decrease incidents of graft versus host disease (GVHD), a sometimes-fatal transplant side effect where donor stem cells attack the patient.

Emory researchers led the phase II trial, following a smaller in-house grant-funded pilot trial that showed abatacept was safe to use in patients. The bigger trial looked at transplant patients receiving stem cells from poorly matched donors, which increases the chance the body will reject the newly infused cells.

When treated with abatacept, about 7% of completely unmatched patients developed life-threatening GVHD; without abatacept, more than twice that number developed GVHD. The numbers were even starker with slightly better, but still poorly matched, donors: 2% developed severe GVHD with abatacept; 30% without it.

The trial results were so significant that the FDA in late 2021 approved abatacept for acute GVHD prevention—the first drug ever approved for this use.

"Homegrown work"

“This was a dramatic effect any way you wanted to slice and dice it,” says Langston. “It’s always really gratifying when you work on something and it actually turns out to lead to something new that’s good for our patients.”

While the study enrolled patients from multiple hospitals around the country, it was led by Emory researchers. The largest cohort of participating patients, about a third of them, were cared for at Winship or the Children’s Healthcare of Atlanta.

“This is very much homegrown work,” says Muna Qayed, MD, MsCR, director of the Blood and Bone Marrow Transplant Program at Children’sAflac Cancer and Blood Disorders Center, Cancer Immunology researcher at Winship and associate professor in the Department of Pediatrics at Emory University School of Medicine. It began in the research lab of former Winship investigator and Children’s faculty member Leslie S. Kean, MD, PhD, now director of the Stem Cell Transplant Center at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Qayed, who joined the multidisciplinary research team as a fellow, is a section chief carrying the work forward.

It was important to the doctors involved to keep the work based at Winship and Children’s, because they are ever-mindful that their medical center is based in a majority-Black community. Due to a complex host of factors, including a primarily white national donor registry, Black patients have the highest transplant complication rates.

“Our patients are considerably less likely to find a perfect match,” says Langston. Black people have about a 23% chance of finding a suitable donor on the registry, compared to about 77% for white people. Abatacept “was a big effect in a group of patients we expect are going to have a harder time with their transplant and have a higher risk that they’re going to die,” Langston says.

Indeed, transplants are arduous and risky even under the best possible circumstances. They involve a lengthy, isolated hospital stay to eliminate a patient’s own diseased bone marrow through high-dose chemotherapy, transplanting donor cells to replace them and then rebuilding immune system capacity. “While it is curative and lifesaving for a number of different types of diseases, it also carries a lot of toxicity,” says Benjamin K. Watkins, MD, director of the Global Oncology Program at the Aflac Cancer and Blood Disorders Center, Discovery and Developmental Therapeutics researcher at Winship and associate professor at Emory University School of Medicine. “It’s an intense process to go through and, unfortunately, many patients don’t survive it.”

This means that any place in the process where doctors can minimize the things that can go wrong along the way, such as GVHD, will improve survival rates. “I believe 100% there are patients I’m seeing in clinic right now who are alive because of abatacept,” Watkins says.

An "incredibly fruitful partnership"

One factor that made the abatacept study’s results so powerful was its inclusion of both pediatric and adult transplant patients.

“It was very deliberate on our part,” says Langston, “that we wanted children to be part of this so that if this became standard practice, whether the FDA endorsed it or not, we had data to say whether it was safe and effective not only in adults but also safe and effective in kids.”

Opening the study to children as young as six years old was not an automatic decision. In fact, youths are often excluded from new drug trials to protect them from unknown outcomes. But the partnership between Winship and CHOA researchers helped make sure all ages were represented.

“GVHD is equally as devastating in kids as it is in adults,” says Qayed. “Whenever we can represent pediatrics within these clinical trials, it speeds up the translation for these findings into the pediatric fields.”

The partnership went deeper than the participant population. The two institutions provided pharmacy support for the entire trial, and both places worked to support the data collection. And the relationships forged during years of intense collaboration created an environment conducive to mentorship, allowing younger clinicians like Qayed and Watkins to grow into more senior roles as their careers progressed.

Now, they are mentoring another generation of rookie researchers as the team builds on abatacept’s FDA approval with ongoing research that explores its potential uses in and beyond transplant.

“This was one of those classic benchto- bedside stories that really started here at Emory,” Langston says. “It’s just been an incredibly fruitful partnership.”

Redd, now retired, is living proof. While there’s no way to tell for sure whether he would have developed GVHD without abatacept, taking it helped ensure his survival.

Redd says the last time he saw Langston, she asked him, “How are you doing?’” He replied, “I’m doing fine; I pretty much do anything I want.’” To which he says she responded, “You do realize this is as good as it gets?”

“I do realize how blessed I am,” he continues. “It was the first time I’d ever been to Emory in my life, and I’ve got nothing but praise for everybody at Emory and their work, and their care.”