Among patients undergoing unrelated-donor (URD) allogeneic hematopoietic cell transplant (HCT), abatacept may help to prevent death due to severe acute graft-vs-host disease (AGVHD), according to research published in the Journal of Clinical Oncology.

While HCT is an effective and potentially curative option among patients with hematologic malignancies, the use of URDs, which are often necessary when patients do not have a human leukocyte antigen (HLA)-matched donor, may lead to AGVHD. Severe AGHD, defined as grade 3 or 4, is potentially life-threatening and is associated with a high rate of nonrelapse mortality.

Preclinical data suggest that abatacept, a T-cell costimulation blockade agent, may help to prevent AGVHD among patients undergoing URD HCT. For this phase 2 trial (ABA2, ClinicalTrials.gov Identifier: NCT01743131), researchers evaluated whether abatacept in conjunction with a calcineurin inhibitor and methotrexate can safely lower the risk of severe AGVHD among patients receiving a 7/8-HLA-matched or 8/8-HLA-matched URD HCT.


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Overall, in the 7/8 cohort, 46 patients were enrolled and 43 received abatacept; in the 8/8 cohort, 148 patients were enrolled, of whom 73 were randomly assigned to receive abatacept and 69 were randomly assigned to receive a placebo. Results from patients in the 7/8 cohort were compared with those of Center for International Blood and Marrow Transplant Research (CIBMTR)-matched controls. Patient characteristics were well balanced between the cohort subgroups.

In the 7/8 cohort, 2.3% of patients in the abatacept group developed severe AGVHD compared with 30.2% (P < .001) in the CIBMTR-matched group. Patients in the abatacept group also had improved 180-day severe AGVHD-free survival (SGFS; 97.7% vs 58.7%, respectively; P < .001).

In the 8/8 cohort, 6.8% of patients in the abatacept group developed severe AGVHD compared with 14.8% in the placebo group (hazard ratio, 0.45; P = .13). Patients in the abatacept group did, however, have improved SGFS compared with that seen in the placebo group (93.2% vs 82%; P = .05).

Safety data with abatacept were not reported in the primary manuscript.

“In summary, the ABA2 trial demonstrated the safety and efficacy of in vivo costimulation blockade with abatacept in preventing both moderate-severe and severe AGVHD after 7/8 URD HCT, with a significant impact on moderate-severe AGVHD and steroid-refractory AGVHD in 8/8 patients,” the authors wrote. “The substantial improvement in survival indicators in the 7/8 cohort suggest that the addition of abatacept could be clinical practice-changing for these otherwise high-risk transplants.”

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Watkins B, Qayed M, McCracken C, et al. Phase II trial of costimulation blockade with abatacept for prevention of acute GVHD. J Clin Oncol. Published online January 15, 2020. doi:10.1200/JCO.20.01086