A prospective clinical trial of GVHD prophylaxis with posttransplant cyclophosphamide and abatacept.

We conducted a prospective randomized clinical trial to investigate the combination of posttransplant cyclophosphamide (PTCy) and abatacept (Aba) for graft-versus-host disease (GVHD) prophylaxis. Patients with hematologic malignancies undergoing an allogeneic transplant from an 8/8 matched related or unrelated donor were randomized 1:1 to tacrolimus and methotrexate (standard-of-care arm [SOC]) or PTCy on days +3 and +4, followed by Aba on an extended schedule: days +5, +14, and +28, and every 4 weeks up to day +168 (PTCy+Aba). All patients received peripherally collected stem cells. The primary end point was moderate and severe chronic GVHD at 1 year. Following US Food and Drug Administration approval of Aba for GVHD prophylaxis leading to change in institutional SOC, the trial was amended to enroll only on the PTCy+Aba arm. A total of 25 patients enrolled on PTCy+Aba, and 15 on SOC. The trial met its primary end point: Kaplan-Meier estimates of moderate and severe chronic GVHD were 0% on the PTCy+Aba and 65.8% on the SOC arm (P < .0001). GVHD-free, relapse-free survival (GRFS) was 62.5% on PTCy+Aba and 24.1% on SOC (P = .010). There were no treatment-related deaths on PTCy+Aba and 2 on SOC. Overall survival (PTCy+Aba, 92%; SOC, 80%; P = .28), disease-free survival (PCTy+Aba, 68%; SOC, 92.9%; P = .105), and infection rates at 1 year were similar. Grade 3/4 acute GVHD rate was 4.2% on PTCy+Aba and 21.4% on SOC (P = .092). PTCy+Aba preserved regulatory T-cell proliferation and increased CD16+CD56dim cytotoxic natural killer cells. In conclusion, PTCy+Aba is well tolerated and associated with reduced chronic GVHD and improved GRFS. This trial was registered at www.ClinicalTrials.gov as #NCT03680092.