FDA Approval Offers Hope for Prevention of Acute Graft-Versus-Host Disease

Leslie Kean, MD, PhD

The U.S. Food and Drug Administration (FDA) today approved a treatment to prevent acute graft-versus-host disease (GVHD) in patients 2 years of age or older receiving a hematopoietic stem cell transplant from a matched or single-HLA-mismatched unrelated donor. The new drug, added to standard regimens, will help many more patients with cancer or blood disorders to undergo stem cell transplants, particularly patients of diverse ethnicities who have more difficulty finding appropriately matched donors in the National Marrow Donor Program (NMDP) registry.

Abatacept, a drug used to treat autoimmune diseases, is the first FDA-approved therapy to prevent acute GVHD after hematopoietic stem cell transplant, and is marketed by Bristol Myers Squibb under the brand name Orencia^®. Acute GVHD is a potentially life-threatening complication in which T cells in the transplanted donor bone marrow attack the recipient’s healthy cells and tissues, causing major damage to the skin, liver, and GI tract.

The FDA approval is based on results from two key studies in patients undergoing stem cell transplant. One was the Phase 2 GVHD-1 trial, also known as ABA2, led by Leslie S. Kean, MD, PhD, director of the Stem Cell Transplant Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center in collaboration with Bristol Myers Squibb. The trial evaluated abatacept when added to a standard-of-care regimen (methotrexate plus a calcineurin inhibitor, either cyclosporine or tacrolimus) for prophylaxis of acute GVHD. Findings were published in January 2021 in the Journal of Clinical Oncology.

The other, confirmatory study, known as GVHD-2, was a non-interventional (observational) study using data from the Center for International Blood and Marrow Transplant Research (CIBMTR). An abstract with the GVHD-2 data was presented December 13 at the 2021 American Society of Hematology Annual Meeting and Exposition.

Expanding the transplant donor pool

Hematopoietic stem cell transplant involves the infusion of donor hematopoietic (blood-forming) stem cells, as well as donor T cells, a type of white blood cell. The GVHD-1 trial involved patients receiving hematopoietic stem cell transplants from unrelated donors. When the donor is unrelated, as many as 70 percent of transplant recipients develop acute GVHD, particularly when donor and recipient are not fully matched on immune factors known as human leukocyte antigens (HLA).

In the GVHD-1 trial, some patients had donors who were matched on 8 of 8 HLA factors, while others were matched on only 7 of 8 factors.

“Patients receiving abatacept demonstrated reductions in severe acute GvHD, and improved survival in transplants involving both 8/8 matched and 7/8 mismatched unrelated donors,” said Kean. “These data suggest that providers can have more confidence in expanding the donor pool for hematopoietic stem cell transplants to include unrelated matched or one-allele-mismatched donors for patients in need.”

The results in the 7/8 mismatched transplants were especially encouraging, as many people in non-white ethnic groups have difficulty finding a full 8/8 match.

“Patients with donors matched on only 7/8 HLA factors have previously had dismal outcomes, with many oncologists not considering these donors, because of the associated risks,” Kean said. “Making these transplants safer will give us the ability to offer life-saving transplants to many more patients.”

“With abatacept’s approval as a preventive option for acute GVHD, we hope hematopoietic stem cell transplant becomes a more accessible option for more patients, particularly those of diverse ethnicities who have lower likelihoods of finding matched donors,” said Steven Devine, MD, Chief Medical Officer of NMDP/Be The Match, and Associate Scientific Director of CIBMTR.

Abatacept curbs the T-cell attack that drives acute GVHD by binding to and inhibiting one of the key costimulatory signals that activates T cells, thereby preventing full T-cell activation.

Abatacept is now available to eligible patients at Dana-Farber/Boston Children's. Learn more about the Stem Cell Transplant Center at Dana-Farber/Boston Children’s.