Approval of abatacept for prophylactic treatment of aGvHD

The U.S Food and Drug Administration (FDA) announced on December 15, 2021, that abatacept has been approved for prophylactic treatment of acute graft-versus-host disease (aGvHD) in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX). This approval is for use in patients from 2 years of age who received a hematopoietic stem cell transplant (HSCT) from a matched or 7/8 human leukocyte antigen (HLA)-mismatched unrelated donor. This is the first agent to be approved for the prevention of aGvHD.¹ Abatacept was previously granted a breakthrough designation for the prevention of aGvHD.

This decision has been made based on data from two studies. The first is GvHD-1 (NCT01743131), a phase II, multicenter, randomized, placebo-controlled trial of patients (N = 186) who were given an 8/8 HLA-matched HSCT and were treated with abatacept or a placebo along with CNI + MTX.

Results from this trial did not show a significant improvement in Grade III–IV aGvHD-free survival at Day 180 in patients receiving abatacept during the trial. However, at Day 180 the overall survival rate was 97% (95% confidence interval [CI], 89–99%) compared with 84% (95% CI, 73–91%) for the patients receiving abatacept compared with the placebo, respectively (hazard ratio, 0.33; 95% CI, 0.12–0.93%). In addition, the Grade II-IV aGvHD-free survival for patients receiving the placebo was 32% (95% CI, 21–43%) compared with 50% (95% CI, 38–61%) for patients treated with abatacept at Day 180 post HSCT (hazard ratio, 0.54; 95% CI, 0.35–0.83%).

The second trial is the GvHD-2 clinical study of 54 patients who received a 7/8 HLA-matched HSCT and were treated with abatacept for aGvHD prophylaxis + CNI + MTX. This group was compared with 162 patients who received only CNI + MTX. The data were provided by the Center for International Blood and Marrow Transplant Research (CIBMTR).

The results of this study showed that at 180 days post HSCT the overall survival rate was 98% (95% CI, 78–100%) for patients treated with abatacept + CNI + MTX compared with 75% (95% CI, 67–82%) for patients who were given CNI + MTX only.

Abatacept acts as a T-cell costimulation blocker and has also been approved for the treatment of rheumatoid arthritis.²