Phase III GRAPPA trial: PTCy vs ATLG as GvHD prophylaxis in URD allo-HSCT

During the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE, Johannes Schetelig presented results from the randomized phase III GRAPPA trial (NCT05153226), comparing post-transplant cyclophosphamide (PTCy)-100 (n = 383) vs anti-T-lymphocyte globulin (ATLG)-30 (n = 257) as graft-versus-host disease (GvHD) prophylaxis in adults undergoing ≥7/8 human leukocyte antigen (HLA)-compatible unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary endpoint was overall survival (OS) and GvHD-free/relapse-free survival (GRFS) was a co-primary endpoint.

Key data: PTCy did not demonstrate non-inferior OS vs ATLG: 2-year OS was 68% with PTCy vs 75% with ATLG (adjusted hazard ratio [aHR], 1.341; 95% confidence interval [CI], 0.999–1.801; non-inferiority test with a 5% margin, p = 0.85; superiority, p = 0.051). There was no significant difference in 2-year GRFS (48% vs 40%; aHR, 0.85; 95% CI, 0.69–1.06; p = 0.16), while 2-year non-relapse mortality (NRM) was higher with PTCy (13% vs 7%; aHR, 1.86; 95% CI, 1.09–3.17; p = 0.02). PTCy was associated with a lower cumulative incidence of Grade 2–4 acute GvHD (aGvHD; aHR, 0.70; 95% CI, 0.51–0.96) and any-grade chronic GvHD (cGvHD; aHR, 0.59; 95% CI, 0.45–0.77). However, PTCy was associated with higher infectious mortality and longer hospital stays compared with ATLG.

Key learning: Non-inferiority of PTCy compared with ATLG was not demonstrated with respect to OS.