Prophylactic Abatacept May Mitigate Disparities in Mismatched Unrelated Donor Transplants

The use of abatacept for graft-versus-host disease (GVHD) prophylaxis could help to reduce racial disparities by abrogating the effect of donor mismatching in unrelated donor stem cell transplantation, according to data published as a Letter to the Editor.

According to the authors, there is limited availability of 8/8 HLA-matched unrelated donors for persons of color (POC), and mismatching is associated with increased risk for acute GVHD, transplant-related mortality, and worse overall survival.

A phase-2 trial compared standard GVHD prophylaxis with a calcineurin inhibitor and short course methotrexate (CNI/MTX) to CNI/MTX plus the co-stimulation blockade agent, cytotoxic T-cell lymphocyte-4immunoglobulin (CTLA4) abatacept. Patients with matched donors were assigned to a randomized placebo arm and those with mismatched donors were assigned to a single-arm, open-label arm.

The study showed reductions in acute GVHD with abatacept in both matched and mismatched patients. According to the researchers, the effects were “especially large” in patients with mismatched donors. Next, the researchers performed a post-hoc analysis of the data comparing outcomes in patients with mismatch unrelated donors receiving CNI/MTX and abatacept to patients with matched unrelated donors receiving CNI/MYX alone.

The cumulative incidence of grade 3/4 acute GVHD by day 100 was 2.3% for the mismatched abatacept group and 14.8% in the matched placebo group (P=0.03). With a median follow-up of 25 months in survivors, the 2-year cumulative incidence of treatment-related mortality was 16.7% in the mismatched abatacept group and 16.1% in the matched placebo group.

“Taken together, these results suggest that addition of abatacept to standard CNI/MTX mitigates the disadvantages of mismatching by greatly reducing the risks of severe acute GVHD and non-relapse mortality without increasing the risk of relapse,” the researchers wrote.