Novel GVHD Prevention Regimen Shows Strong Results Without Standard Immunosuppressants

A novel three-drug regimen for preventing graft-versus-host disease after allogeneic stem cell transplantation without conventional calcineurin or mTOR inhibitors has shown promising efficacy and tolerability, according to interim results from the ABC phase 1/2b clinical trial. The regimen combining posttransplant cyclophosphamide, bortezomib, and abatacept led to low GVHD incidence and favorable survival outcomes while enabling earlier introduction of posttransplant maintenance therapies.

Interim results of the ABC trial (NCT06681922) presented at the 2026 European Blood and Marrow Transplantation Society conference demonstrated that the calcineurin inhibitor-free approach achieved strong results. By day +180, the estimated cumulative incidence of grade 2 to 4 acute GVHD was 4.8% in the matched donor cohort and 18.5% in the mismatched cohort, with no grade 3 or 4 events occurring in either group. At one year, moderate and severe chronic GVHD incidence was 10.2% and 12.5% in the matched and mismatched cohorts, respectively.

The trial enrolled 60 of an intended 74 patients across two cohorts: matched related or unrelated donor transplants and mismatched (7/8) unrelated donor transplants of peripheral blood stem cells. The study population had a median age of 59 years, with acute myeloid leukemia representing the most common diagnosis. The primary end point was the incidence of grade 2 to 4 acute GVHD by day 120.

Survival outcomes were favorable, with one-year overall survival at 91.3%, progression-free survival at 78.2%, and GVHD- and relapse-free survival at 70.9%. The one-year cumulative incidence of relapse was 17.7%, and treatment-related mortality was 5.2%. At two years, these were 20.9% and 13.6%, respectively. There were five cases of disease relapse and six of treatment-related mortality.

A key secondary finding concerned the impact of reducing the posttransplant cyclophosphamide dose from 50 mg/kg to 37.5 mg/kg on days +3 and +4. In the 35 patients receiving the lower dose, median time to neutrophil engraftment was 15 days compared with 17 days in the 25 patients who received full-dose cyclophosphamide, and median platelet engraftment occurred at 22 versus 25.5 days. No primary or secondary graft failure was observed in either group, and full donor chimerism was achieved in 94.8% of patients by day +100.

Importantly, reducing the cyclophosphamide dose did not appear to compromise immune reconstitution. Recovery of CD3+, CD4+, CD8+, and CD19+ lymphocyte subsets was comparable between the two dose groups at days +30, +100, and +180. Dose reduction did not appear to significantly affect GVHD incidence.

The regimen was completed by day +28 following transplant, representing a short-duration approach that aims to reduce toxicity and enable earlier posttransplant maintenance initiation. The trial did not include calcineurin inhibitors such as tacrolimus or cyclosporine or mTOR inhibitors such as sirolimus, which are standard components of most current prophylaxis regimens but carry significant toxicity and complicate the early introduction of posttransplant maintenance therapies.