A prospective clinical trial of GVHD prophylaxis with Post-Transplant Cyclophosphamide and Abatacept Open Access

• PTCy/abatacept is associated with less chronic GVHD and a favorable GVHD-Free, Relapse-Free Survival compared to methotrexate/tacrolimus.

• PTCy and abatacept without a calcineurin inhibitor can be used for GVHD prophylaxis.

We conducted a prospective randomized clinical trial to investigate the combination of post-transplant cyclophosphamide (PTCy) and abatacept for 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 (SOC arm) or PTCy on days +3 and +4 followed by abatacept on an extended schedule: days +5, +14, +28 and every 4 weeks up to D+168 (PTCy+aba arm). All patients received peripherally collected stem cells. The primary endpoint was moderate and severe chronic GVHD at one year. Following Food and Drug Administration (FDA) approval of abatacept for GVHD prophylaxis leading to change in SOC, we amended our trial and subsequently only enrolled onto the PTCy+aba arm. 25 patients were treated on PTCy+aba and 15 on SOC arm. The trial met its primary endpoint: Kaplan-Meier estimates of moderate/severe chronic GVHD were 0% on the PTCy+aba and 65.8% on the SOC arm (p < 0.0001). GVHD-Free, Relapse-Free Survival (GRFS) was 62.5% on PTCy+aba and 24.1% on SOC (p=0.010). There were no treatment related deaths on PTCy+aba and two on SOC. There was no difference in the overall survival rates (92% aba, 80% SOC, p=0.28), disease free survival (68% aba, 92.9% SOC, p=0.105) and infection at one year. Grade III/IV acute GVHD rate was 4.2% on PTCy+aba and 21.4% on SOC (p=0.092). Proliferation of regulatory T-cells was preserved on PTCy+aba compared to SOC and PTCy and abatacept treatment was associated with increased CD16+CD56dim cytotoxic NK cells. In conclusion, the combination of PTCy and abatacept is well tolerated and associated with reduced chronic GVHD and a favorable GRFS rate. This trial was registered at www.ClinicalTrials.gov as #NCT03680092.