ATLANTA (Dec. 20, 2021) – Based on compelling results from a clinical trial with participation from Children’s Healthcare of Atlanta and Emory University School of Medicine, the first drug for the prevention of acute graft versus host disease (GVHD) is now approved by the U.S. Food and Drug Administration (FDA) for use in adults and children as young as two-years-old undergoing unrelated donor blood and marrow transplant (BMT).
Now available to patients at Children’s, abatacept was previously tested in a seven-year, multi-site national trial led at Children’s by Muna Qayed, MD, MSc, and Benjamin K. Watkins, MD, Hematologists/Oncologists at the Aflac Cancer and Blood Disorders Center. Findings, recently published in the Journal of Clinical Oncology, showed abatacept significantly reduced the risk of severe acute GVHD and improved survival among children and adults undergoing unrelated donor BMT for hematologic cancer. Acute GVHD occurs after stem cell transplantation, when the donated cells turn against the patient or host and begin attacking the patient’s organs. Severe GVHD is life-threatening and represents a major cause of death after transplantation.
“The major impact of abatacept is making unrelated donor transplant safer, particularly for patients who do not have a full match,” said Dr. Qayed, Director of the BMT Program for the center and an Associate Professor of Pediatrics at Emory. “The chance of finding a full match in the registry is less than 50% for people of color, so this approach will safely broaden the donor pool for patients who need a transplant.” Some groups, including a large portion of African Americans, have a less than 30% chance of finding a matched donor. When abatacept was used with mismatched donors, the outcomes improved almost to the level of matched donors, meaning abatacept may lessen the disparities in outcomes for people of color, according to a paper recently published by Drs. Watkins and Qayed in Blood Advances.
Abatacept has been used in over 30 Children’s patients to date with excellent outcomes consistent with the findings of the Phase 2 clinical trial known as ABA2 that led to FDA approval. The trial began in 2013 with funding from the National Institutes of Health (NIH) and involved 14 other sites in the U.S. and Canada, including the Winship Cancer Center at Emory. 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 and survival.
“Compared to 30% for the control group, the incidence of severe disease dropped to only 3% in our ABA2 trial for the abatacept treated group,” said Dr. Watkins, Director of Global Oncology Program for the center and Assistant Professor of Pediatrics at Emory.
BMT often offers the last chance for a cure for children with hematologic cancers like leukemia and lymphoma. During a BMT a donor’s healthy stem cells are used to replace the patient’s dysfunctional bone marrow stem cells responsible for their cancer. But for the donor immune system not to attack the patient’s body during the process, human leukocyte antigen (HLA) proteins, or markers the immune system uses to recognize which cells belong to your body, must match as closely as possible.
Siblings have a one in four chance of being HLA-matched, resulting in fewer than 25% of patients having a perfect match. These individuals often utilize the National Marrow Donor Program through BeTheMatch.org to identify unrelated donors.
“Up until now, there has not been a groundbreaking drug to change the risk of getting GVHD in the first place,” said Dr. Watkins. “Abatacept has the potential to save many lives by preventing this devastating disease.”
Five clinical trials at Children’s have evaluated abatacept in unrelated donor transplant. Drs. Qayed and Watkins will soon begin the ABA3 trial as a follow up study. The treatment abatacept is also used for rheumatoid arthritis.
In addition to funding from the NIH, the ABA2 trial was completed with support from Bristol Myers Squibb and the CURE Childhood Cancer Foundation. Dr. Watkins and Dr. Qayed are co-first authors on the publication describing the results. 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. The ABA2 trial was based on a pilot trial published in 2013 and funded by a grant from the CURE Childhood Cancer Foundation and by a Pediatric Hematology/Oncology Research Grants (PHORG) award from the Aflac Cancer and Blood Disorders Center.