In Phase 2 Trial, Orencia Prevented Graft-Versus-Host Disease After Stem Cell Transplant

In Phase 2 Trial, Orencia Prevented Graft-Versus-Host Disease After Stem Cell Transplant

The rheumatoid arthritis medicine Orencia (abatacept) is a promising approach to prevent graft-versus-host disease (GvHD) in patients receiving hematopoietic stem cell transplants from unrelated donors, a new Phase 2 clinical trial shows.

When added to the standard regimen used to prevent GvHD in pediatric and adult patients, the drug reduced the incidence of this life-threatening condition from 32 to 3 percent.

The findings were recently revealed during the 59th American Society of Hematology (ASH) Annual Meeting. Leslie Kean, MD, the trial’s principal investigator, presented the study, “T Cell Costimulation Blockade with Abatacept Nearly Eliminates Early Severe Acute Graft Versus Host Disease after HLA-Mismatched (7/8 HLA Matched) Unrelated Donor Transplant, with a Favorable Impact on Disease-Free and Overall Survival.”

Stem cell transplant is one of the most effective curative treatments for blood cancer patients. However, it comes with great risk of life-threatening infection and GvHD. GvHD happens when the transplanted T-cells — cells that fight infections and cancer — see the recipient’s body as foreign and react against it.

The therapeutic strategies to prevent GvHD commonly rely on the suppression of the immune system, which can lead to severe infections.

Orencia, developed by Bristol-Myers Squibb to treat patients with rheumatoid arthritis, was shown to suppress the activation of T-cells, suggesting it could help prevent GvHD.

The ongoing trial (NCT01743131), sponsored by the Seattle Children’s Research Institute, is evaluating if the addition of Orencia to the standard drug treatment to prevent GvHD can provide better protection against the disease, without causing more infections.

The multi-center, randomized, double-blind, placebo-controlled trial included two patient groups.

The first group included 43 pediatric and adult patients who received four doses of Orencia, along with a calcineurin inhibitor and methotrexate (CNI/MTX), after receiving a transplant from a mismatched, unrelated donor.

The results were compared to data from a national database of matched patients receiving two common GvHD treatments — CNI/MTX, or CNI/MTX plus anti-thymocyte globulin (+ATG).

Only 3 percent of patients receiving Orencia experienced severe acute GvHD, compared to 32 percent in CNI/MTX, and 22 percent in +ATG treatments. Also, patients receiving Orencia showed no major uncontrolled infections, a significant improvement in transplant-related mortality, and no increase in disease relapse.

Orencia showed significant survival advantages at one year post-transplant compared to the other two treatments. While 79 percent of patients receiving Orencia were still disease-free one year after the transplant, the figures were 50 percent and 63 percent, respectively, for the other two treatments.

Also, 85 percent of patients given Orencia were alive after the first year, compared to 57 percent in CNI/MTX and 68 percent in +ATG treatments.

“Given the serious threat of graft-versus-host disease, new approaches to make stem cell transplants safer for patients remain a critical unmet need,” Kean said in a press release. “To see such striking results in patients at extremely high risk for graft-versus-disease is incredibly encouraging.”

“As a transplant physician, it’s beyond heartbreaking to witness a patient develop severe acute graft-versus-host disease after having their leukemia cured through bone marrow transplant,” Kean said.

“To have a therapy at our disposal that safely targets just the T cells causing graft-versus-host disease would represent a major step forward in stem cell transplantation. It not only offers new hope that we can prevent graft-versus-host disease upfront, but that we can also significantly improve outcomes for patients requiring high-risk transplants,” she concluded.

Results from the second group of 140 patients with matched unrelated donor transplants are expected in the next six months.