The FDA approved abatacept plus immunosuppressant therapy for the prevention of acute graft versus host disease (aGVHD) in patients two years of age and older undergoing hematopoietic stem cell transplantation, making it the first approved prophylactic treatment for the deadly complication.
Abatacept, a selective T cell costimulation modulator, was first approved in 2005 and has previously earned indications for moderate to severe rheumatoid arthritis, moderate to severe juvenile idiopathic arthritis, and active psoriatic arthritis.
Under this new indication, abatacept—in combination with a calcineurin inhibitor and methotrexate—can be administered to patients age 6 and older at a 10 mg/kg dose during a 60-minute infusion one day before hematopoietic stem cell transplant, followed by a dose on days 5, 14, and 28 after transplant. As for kids ages 2-6 years, a 15 mg/kg dose can be administered the day before transplant, followed by 12 mg/kg doses on days 5, 14, and 28 post-transplant.
“Acute graft versus host disease can affect different parts of the body and become a serious post-transplant complication,” said 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, in a statement. “By potentially preventing the disease, more patients may successfully undergo bone marrow or stem cell transplantation with fewer complications.”
This approval was based on data from a pair of clinical trials: GVHD-1 and GVHD-2.
The double-blind, placebo-controlled GVHD-1 trial randomized 186 patients who underwent stem cell transplantation from a matched unrelated donor to either abatacept or placebo in combination with immunosuppressive drugs. The study outcomes were severe (grade III-IV) aGVHD-free survival, overall survival, and moderate-severe (grade II-IV) aGVHD-free survival six months post-transplant.
“While severe aGVHD-survival was not significantly improved in patients who received [abatacept] (87%) compared to patients who received a placebo (75%), patients who received [abatacept] saw a 97% overall survival rate compared to 84% for patients who received a placebo,” the FDA wrote. “For moderate-severe aGVHD-free survival, patients who received [abatacept] saw a 50% rate compared to 32% for patients who received a placebo.”
GVHD-2 was a registry-based clinical study “conducted using real world data from the Center for International Blood and Marrow Transplant Research in patients who underwent stem cell transplantation from a mismatched unrelated donor,” the agency explained. “This study analyzed outcomes of 54 patients treated with [abatacept] for the prevention of aGVHD, in combination with standard immunosuppressive drugs, versus 162 patients treated with standard immunosuppressive drugs alone. The study measured overall survival six months after transplantation. Patients who received [abatacept] saw a 98% overall survival rate compared to 75% for patients who received standard immunosuppression alone.”
The most common adverse events linked to abatacept use for GVHD included anemia, hypertension, cytomegalovirus reactivation or infection, fever, pneumonia, nosebleed, decreased CD4 lymphocyte counts, high levels of magnesium in the blood, and acute kidney injury. The FDA also noted that patients on the drug should be monitored for Epstein-Barr virus reactivation and receive prophylactic treatment for Epstein-Barr prior to treatment and for six months post-transplant.
Abatacept is manufactured by Bristol Myers Squibb.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 254
Topic ID: 253,254,254,730,118,192,725,925