Orencia First Drug FDA Approved for the Prevention of Acute Graft-versus-Host Disease

Web Exclusives - FDA Approvals

On December 15, 2021, the FDA accelerated the approval of abatacept (Orencia; Bristol Myers Squibb), a selective T-cell co-stimulation modulator, for the prophylaxis of acute graft-versus-host disease (GVHD), in combination with a calcineurin inhibitor and methotrexate, in patients aged ≥2 years undergoing hematopoietic stem-cell transplantation (HSCT) from a matched or 1 allele–mismatched unrelated donor. The FDA granted abatacept breakthrough therapy and orphan drug designations for this indication.

Abatacept is currently approved for the treatment of rheumatoid arthritis, and is the first drug ever to receive FDA approval for the prevention of acute GVHD in patients undergoing HSCT.

This approval was based on the results of 2 studies of patients aged ≥6 years undergoing HSCT from a matched or a 1 allele–mismatched unrelated donor.

The GVHD-1 study was a randomized (1:1), double-­blind, placebo-controlled clinical trial of patients who underwent an 8 of 8 HLA-matched HSCT and received abatacept or placebo in combination with a calcineurin inhibitor and methotrexate.

The overall survival (OS) rate at day 180 after HSCT was 97% for patients who received abatacept versus 84% for patients who received a placebo (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.12-0.93).

By disease severity, the rate of severe (grade III or IV) acute GVHD–free survival, which was assessed at day 180 after transplant, was not significantly improved with abatacept compared with placebo (HR, 0.55; 95% CI, 0.26-1.18). By contrast, at day 180 after HSCT, the moderate-severe (grade II-IV) acute GVHD–free survival rate was 50% for patients who received abatacept versus 32% for patients who received a placebo (HR, 0.54; 95% CI, 0.35-0.83).

The second study was GVHD-2, a registry-based study that used clinical data from the Center for International Blood and Marrow Transplant Research (CIBMTR) in patients who underwent a 7 of 8 HLA-matched HSCT between 2011 and 2018. This study analyzed data of 54 patients who had received abatacept for the prophylaxis of acute GVHD, in combination with a calcineurin inhibitor and methotrexate, versus 162 patients who were randomly selected from the CIBMTR registry and had received the combination of a calcineurin inhibitor plus methotrexate but without abatacept.

The OS rate at day 180 after HSCT was 98% (95% CI, 78%-100%) for patients who received abatacept plus a calcineurin inhibitor and methotrexate versus 75% (95% CI, 67%-82%) for patients who received the combination of a calcineurin inhibitor and methotrexate alone.

The most common (≥10%) adverse reactions with abatacept used for the prophylaxis of acute GVHD include anemia, hypertension, cytomegalovirus (CMV) reactivation or infection, pyrexia, pneumonia, epistaxis, decreased CD4 lymphocytes, hypermagnesemia, and acute kidney injury.

Patients should receive antiviral prophylaxis for Epstein-Barr virus infection before starting treatment with abatacept and for 6 months posttransplant, and be monitored for CMV infection or reactivation for 6 months after transplant.

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Last modified: March 14, 2022
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