PTCy Fails to Translate GVHD Reduction to Survival Advantage Vs ATG

Johannes Schetelig, MD, MSc, of director of medical research at DKMS; as well as a professor at Technical University Dresden, shares unexpected results from a large randomized controlled trial presented at the European Hematology Association Annual Congress.The study compared 2 prominent strategies for graft-vs-host disease (GVHD) prophylaxis in patients undergoing allogeneic stem cell transplantation: anti T-lymphocyte globulin (ATLG or ATG) vs posttransplant cyclophosphamide (PTCy).

The trial's findings challenged investigator expectations given the widespread benefit seen with PTCy over the past years.Although PTCy behaved as anticipated, demonstrating superior potency in suppressing acute and chronic GVHD of any grade, including moderate-to-severe forms, this GVHD suppression did not yield a survival benefit. Both arms demonstrated no statistical difference regarding the risk of disease relapse. However, the PTCy cohort exhibited a significantly higher risk of nonrelapse mortality (NRM). This elevated NRM was driven by an increased incidence of infectious deaths in patients who did not suffer from active GVHD.

The difference in toxicity profiles translated into a meaningful divergence in survival outcomes. At the 2-year mark, the overall survival rate reached 75% for patients in the ATLG arm compared with 68% for those in the PTCy arm. This survival gap was underpinned by a low 2-year NRM of just 7% with ATG use, contrasted against a 13% NRM rate in the PTCy cohort. The remarkable safety margin of ATG, driven by fewer fatal infectious complications, provided a strong statistical signal for potentially improved overall survival.

Consequently, the trial was unable to establish the noninferiority of PTCy. Dr. Schetelig concludes that ATG, administered at a dose of 30 mg/kg across days -3, -2, and -1 in combination with tacrolimus and mycophenolate mofetil should remain the standard of care for patients receiving stem cell transplants from matched unrelated donors in Europe.

REFERENCE

1. Schetelig J, Stelljes M, Kunadt D, et al. GVHD prophylaxis including ATG remains standard of care for HLA-compatible unrelated donor hematopoietic cell transplantation: results from a large randomized controlled trial comparing ATG and PTCy. Presented at: the European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract LB5009.