The Food and Drug Administration (FDA) has approved Orencia (abatacept), in combination with a calcineurin inhibitor and methotrexate, for the prevention of acute graft versus host disease (aGVHD) in patients 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor.
The approval was based on data from the multicenter, randomized, double-blind, placebo-controlled phase 2 GVHD-1 trial (ClinicalTrials.gov Identifier: NCT01743131) and real world evidence from a registry trial. The GVHD-1 trial evaluated abatacept, a selective T-cell costimulation modulator, for the prevention of severe aGVHD when added to a standard GvHD prophylactic regimen in patients 6 years of age and older who underwent HSCT from a matched or 1 allele-mismatched unrelated donor.
The GVHD-1 trial included 2 cohorts: an open-label, single arm cohort of 43 patients who underwent a 7 of 8 Human Leukocyte Antigen (HLA)-matched HSCT (7/8 cohort), and a randomized, double-blind, placebo-controlled study of patients who underwent an 8 of 8 HLA-matched HSCT and received either abatacept or placebo in combination with a calcineurin inhibitor and methotrexate (8/8 cohort).
Findings from the 8/8 cohort showed that severe (grade III-IV) aGVHD-free survival was not significantly improved at day 180 post-transplant in patients treated with abatacept vs placebo (87% vs 75%, respectively). However, the overall survival rate in the abatacept arm was 97% (95% CI, 89-99) compared with 84% (95% CI, 73-91) for the placebo arm.
In an exploratory analysis of the 7/8 cohort of abatacept-treated patients, the rates of grade III-IV GVHD-free survival, grade II-IV GVHD-free survival, and overall survival at day 180 post transplantation were found to be 95% (95% CI, 83-99), 53% (95% CI, 38-67), and 98% (95% CI, 85-100), respectively.
“In the GVHD-1 trial, abatacept demonstrated improved severe (grade III-IV) aGvHD-free survival in 7/8 mismatched unrelated donor transplant and associated mortality,” said Leslie Kean, MD, director of the Stem Cell Transplantation Center at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “From these results, providers may also have more confidence in expanding the donor pool to include unrelated matched or 1 allele-mismatched donors for patients in need.”
The registry-based clinical study was conducted using real world data from the Center for International Blood and Marrow Transplant Research in patients 6 years of age and older who underwent HSCT from a 1 allele-mismatched unrelated donor between 2011 and 2018. The study evaluated abatacept in combination with a calcineurin inhibitor and methotrexate compared with a calcineurin inhibitor plus methotrexate alone for the prevention of aGVHD. Results showed an overall survival rate of 98% (95% CI, 78-100) at day 180 for the abatacept group compared with 75% (95% CI, 67-82) for the calcineurin inhibitor plus methotrexate group.
The most common adverse reactions observed in aGVHD trials were anemia, hypertension, cytomegalovirus (CMV) reactivation/CMV infection, fever, pneumonia, nosebleed, decreased CD4 lymphocytes, increased levels of magnesium in the blood and acute kidney injury.
Orencia is also indicated for the treatment of rheumatoid arthritis, psoriatic arthritis, and polyarticular juvenile idiopathic arthritis.
- FDA approves first drug to prevent graft versus host disease. News release. US Food and Drug Administration. December 15, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-prevent-graft-versus-host-disease.
- US Food and Drug Administration approves Orencia® (abatacept) in combination with a calcineurin inhibitor and methotrexate for the prevention of acute graft versus host disease (aGvHD). News release. December 15, 2021. https://www.businesswire.com/news/home/20211213006061/en/U.S.-Food-and-Drug-Administration-Approves-Orencia%C2%AE-abatacept-in-Combination-with-a-Calcineurin-Inhibitor-and-Methotrexate-for-the-Prevention-of-Acute-Graft-Versus-Host-Disease-aGvHD.
- Orencia. Package insert. Bristol-Myers Squibb; 2021. Accessed December 15, 2021. https://packageinserts.bms.com/pi/pi_orencia.pdf.