ABC phase I/IIb interim analysis: PTCy dose reduction in calcineurin- and mTOR inhibitor-free GvHD prophylaxis

During the 52nd Annual Meeting of the European Society for Blood and Marrow Transplantation, March 22–25, 2026, Madrid, ES, A Samer Al-Homsi presented interim results from the phase I/IIb ABC trial (NCT06681922). Post-transplant cyclophosphamide (PTCy) dose reduction was evaluated in patients receiving PTCy + bortezomib + abatacept (ABC regimen) as calcineurin- and mammalian target of rapamycin (mTOR) inhibitor-free graft-versus-host disease (GvHD) prophylaxis. A total of 60 adults with hematologic malignancies were enrolled; 25 received PTCy 50 mg/kg/dose (full-dose) and 35 received PTCy 37.5 mg/kg/dose (reduced dose). The primary endpoint was incidence of Grade 2–4 acute GvHD (aGvHD).

Key data: By Day +180 post-allogeneic hematopoietic stem cell transplantation (allo-HSCT), the estimated cumulative incidence (ECI) of Grade 2–4 aGvHD was 4% with full-dose PTCy vs 11.8% with reduced-dose PTCy (p = 0.29); the ECI of moderate and severe chronic GvHD (cGvHD) at 1 year was 12% and 9.47%, respectively (p = 0.87). One‑year overall survival (OS), progression-free survival (PFS), and GvHD-free, relapse-free survival (GRFS) were 91.3%, 78.2%, and 70.9%, respectively. Reducing PTCy dosing accelerated neutrophil (15 vs 17 days; p = 0.004) and platelet engraftment (22 vs 25.5 days; p = 0.04) without graft failure. There were no significant differences in CD3+, CD4+, or CD8+ cell recovery between the two PTCy groups.

Key learning: The ABC regimen is an effective, short duration, and non-toxic calcineurin- and mTOR inhibitor-free GvHD prophylaxis strategy. Lower-dose PTCy was associated with faster engraftment without a significantly negative impact on GvHD incidence.