FDA Approves Abatacept for the Prevention of Acute GVHD

FDA

The FDA has approved abatacept (Orencia) for the prophylaxis of acute graft-versus-host disease (aGVHD), in combination with certain immunosuppressants.¹

Abatacept is the first agent to receive regulatory approval for prevention of this condition, and the decision was supported by real-world evidence as a component detailing its clinical efficacy.

“Acute graft versus host disease can affect different parts of the body and become a serious post-transplant complication,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, stated in a press release. “By potentially preventing the disease, more patients may successfully undergo bone marrow or stem cell transplantation with fewer complications.”

Thedouble-blind, placebo-controlled GGVHD-1 trial compared the use of abatacept with placebo in a total of 186 patients who underwent stem cell transplantation from a matched unrelated donor. All patients also received immunosuppressive drugs. The research measured severe, defined as grade III to IV, aGVHD-free survival, overall survival (OS), and moderate-severe, defined as grade II to IV, aGVHD-free survival 6 months following transplantation.

Results showed that although abatacept did not significantly improve GVHD-survival vs placebo, at 87% vs 75%, respectively, it did improve OS rate, at 97% and 84%, respectively. With regard to moderate-severe aGVHD-free survival, patients in the investigative arm experienced a 50% rate vs 32% for those in the control arm.

Additional efficacy evidence came from the registry-based, GVHD-2 study, which leveraged real-world findings from the Center for International Blood and Marrow Transplant Research in patients who underwent stem cell transplantation from a mismatched unrelated donor.

In this effort, investigators evaluated outcomes from a total of 54 patients who recieved abatacept to prevent aGVHD, in combination with standard immunosuppressive drugs, compared with 162 patients who received standard immunosuppressive drugs alone. The study measured OS at 6 months post transplantation. OS rates in the investigative and control arms were 98% and 75%, respectively.

Regarding safety, the toxicities that were most frequently reported with abatacept included anemia, hypertension, cytomegalovirus (CMV) reactivation/CMV infection, fever, pneumonia, nosebleed, decreased levels of CD4 lymphocytes, increased levels of magnesium in the blood, and acute kidney injury.

The FDA also noted that those who receive the agent should be monitored for Epstein-Barr virus reactivation per institutional practices and they should receive preventative medication for Epstein-Barr virus infection prior to treatment initiation and for 6 months following transplantation. Patients should also be monitored for CMV infection/reactivation for 6 months after transplant.

Reference

1. FDA approves first drug to prevent graft versus host disease. News release. FDA; December 15, 2021. Accessed December 15, 2021. https://bit.ly/33zfoxR