Trial Shows Abatacept Reduces Risk for Acute GVHD

ATLANTA (Jan. 15, 2021) – The drug abatacept was shown to significantly reduce the risk of acute graft-versus-host disease (GVHD) among children and adults undergoing unrelated donor blood and marrow transplant (BMT) for hematologic cancer during a seven-year, multisite trial. Led by Benjamin K. Watkins, MD, and Muna Qayed, MD, hematologists and oncologists at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, findings from the trial were published today in the Journal of Clinical Oncology and led to Food and Drug Administration (FDA) breakthrough status for the therapy.

“In severe acute GVHD, almost half the patients will die, but the incidence of severe disease dropped to only 3% in our abatacept treated group, compared to 30% for the control group—so really a striking response,” said Dr. Watkins, who is also an Assistant Professor in the Emory University School of Medicine Department of Pediatrics.

Kids with hematologic cancers like leukemia and lymphoma have malfunctioning blood cells due to the cancer’s effects on their bone marrow and lymphatic system. A common treatment is a bone marrow transplant, in which a donor’s healthy stem cells are delivered intravenously over several weeks to help restore bone marrow stem cells. But for the patient’s body to accept, and not reject, the donor transplant, human leukocyte antigen (HLA) proteins, or markers the immune system used to recognize which cells belong to your body, must match as closely as possible.

Siblings have a 1 in 4 chance of being HLA-matched, resulting in fewer than 25% of patients having that perfect match. These individuals utilize the National Marrow Donor Program through to identify unrelated donors.

“Some groups, such as African Americans, have a less than a 20% chance of finding a perfect match,” Dr. Watkins said. “For these patients, physicians must look for mismatched unrelated donors. This comes with tremendous risks, including high rates of acute GVHD.”

Acute GVHD occurs after stem cell transplantation, when the donated cells turn against the patient or host and begin attacking the patient's organs. In the most severe forms, half of patients die.

The Phase 2 trial at Children’s, led by Drs. Watkins and Qayed, began in 2013 with funding from the National Institutes of Health (NIH). Of the 186 patients enrolled with hematologic malignancies, 30% were pediatric patients under age 21. The trial involved 14 other sites in the U.S. and Canada, including the Winship Cancer Center at Emory University. There were two arms of the study. One was a randomized, double-blind, placebo-controlled group with 143 perfectly matched unrelated donors. The second included 43 patients who were mismatched unrelated donors on seven out of eight HLA proteins, all receiving abatacept.

Results showed the addition of four total doses of abatacept given within one month after transplant had a significant improvement in rates of acute GVHD. In the matched unrelated donor arm, the incidence of severe disease was 7% with abatacept, compared to 15% in the placebo treated. The results were most profound in the mismatched unrelated donor arm, in which the incidence of severe disease dropped to only 3% in the abatacept treated group, compared to 30% for the control group. Furthermore, the overall survival of two years after transplant significantly improved with 74% of patients treated with abatacept surviving, compared to just 45% of control patients.

“Not only were we preventing acute GVHD, but more patients were also living, likely because they weren’t developing it,” said Dr. Watkins.

The striking results led to an FDA breakthrough therapy designation for abatacept for the prevention of GVHD in unrelated donor transplant for both matched and mismatched groups. The designation expedites the development and review of new medicines that have a potential for significant impact on patients with life-threatening illnesses.

“We hope that with the addition of abatacept, we’re now going to make transplant an option for a greater number of people, especially those with the highest risk in certain ethnic and racial groups,” said Dr. Watkins.

The study led to another Phase 2 trial with extended dosing of abatacept and multiple other studies using abatacept in different diseases, including two at the Aflac Cancer and Blood Disorders Center.

“Up until now, there has not been a groundbreaking drug to change the risk of getting GVHD in the first place,” Dr. Watkins said. “Abatacept has the potential to save many lives by preventing this devastating disease.”

The trial was completed with support from Bristol Myers Squibb. Leslie S. Kean, MD, PhD, and John Horan, MD, MPH, of Boston Children’s, are senior authors on the paper, along with Amy Langston, MD, of the Winship Cancer Center. Dr. Qayed is also an Associate Professor at Emory University and co-first author with Dr. Watkins.

About The Aflac Cancer and Blood Disorders Center of Children’s

The Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta is a national leader among childhood cancer, hematology, and blood and marrow transplant programs, serving children and young adults. Recognized as one of the top childhood cancer centers in the country by U.S. News & World Report, the Aflac Cancer and Blood Disorders Center cares for more than 500 newly diagnosed cancer patients and treats nearly 2,000 unique sickle cell disease patients each year. Our program offers patients access to more than 380 clinical trials, including 28 innovative Aflac Cancer and Blood Disorders Center investigator-initiated trials. Visit for more information.

About Emory University School of Medicine

About Emory University School of Medicine
Emory University School of Medicine is a leading institution with the highest standards in education, biomedical research and patient care, with a commitment to recruiting and developing a diverse group of students and innovative leaders. Emory School of Medicine has more than 3,400 full- and part-time faculty, 592 medical students, 497 allied health students in five programs, 1,388 residents and fellows in 115 accredited programs, and 92 MD/PhD students. Medical school faculty received $588.4 million in external research funding in fiscal year 2022. The school is best known for its research and treatment in infectious disease, brain health, heart disease, cancer, transplantation, orthopaedics, pediatrics, renal disease, ophthalmology and geriatrics.

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