In a phase II trial (ABA2) reported in the Journal of Clinical Oncology, Watkins et al found that the addition of T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)–based graft-vs-host disease prophylaxis resulted in reduced rates of acute graft-vs-host disease in patients with hematologic malignancies receiving unrelated donor hematopoietic cell transplantation (HCT).
Study Details
The U.S. multicenter trial consisted of two cohorts. In a double-blind cohort, 142 patients with 8/8-human leukocyte antigen (HLA)-matched unrelated donor (8/8 patients) were randomly assigned to receive four doses of abatacept at 10 mg/kg on days −1, 15, 114, and 128 plus CNI/MTX (n = 73) or placebo plus CNI/MTX (control group, n = 69). In a single-arm cohort, 43 patients with 7/8-HLA-mismatched unrelated donor (7/8 patients) received abatacept plus CNI/MTX and were compared with matched Center for International Blood and Marrow Transplant Research (CIBMTR) controls who received CNI/MTX without antithymocyte globulin (n = 127).
Patients were enrolled between March 2013 and November 2016. The primary endpoint was severe (grade 3–4) acute graft-vs-host disease at day 100.
“Adding abatacept to unrelated donor HCT was safe, reduced acute graft-vs-host disease, and improved severe graft-vs-host disease–free survival. These results suggest that abatacept may substantially improve acute graft-vs-host disease–related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.”— Watkins et al
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Key Findings
Median follow-up was 716 days in the 8/8 patient cohort. Rates of grade 3–4 acute graft-vs-host disease at day 100 were 6.8% in the abatacept group vs 14.8% in the control group (hazard ratio [HR] = 0.45, P = .13). Rates of grade 2–4 acute graft-vs-host disease were 44.8% vs 63.7% (HR = 0.53, P = .006). Severe graft-vs-host disease–free survival at day 180 was 93.2% vs 82% (P = .05). Rates of mild/severe chronic graft-vs-host disease at 1 year were 51.9% vs 45.3 (P = .55). No significant differences between groups were observed in 2-year rates of relapse, relapse-free survival, nonrelapse mortality, or overall survival.
Median follow-up was 708 days in the 7/8 patient cohort. Rates of grade 3 to 4 acute graft-vs-host disease at day 100 were 2.3% in the abatacept group compared with 30.2% in the matched CIBMTR cohort (P < .001). Rates of grade 2 to 4 acute graft-vs-host disease were 41.9% vs 53.2% (P = .028). Severe graft-vs-host disease–free survival at day 180 was 97.7% vs 58.7% (P < .001).
Flow cytometric analysis showed significant preservation of relative proportions of naive CD4-positive T cells during hematologic reconstitution in abatacept patients irrespective of degree of HLA matching, with preservation being more marked among patients not experiencing grade 3–4 acute graft-vs-host disease.
The investigators concluded, “Adding abatacept to unrelated donor HCT was safe, reduced acute graft-vs-host disease, and improved severe graft-vs-host disease–free survival. These results suggest that abatacept may substantially improve acute graft-vs-host disease–related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.”
Leslie S. Kean, MD, PhD, of the Stem Cell Transplantation Program, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Institutes of Health; National Heart, Lung, and Blood Institute; Bristol Myers Squibb; and others. For full disclosures of the study authors, visit ascopubs.org.
