GVHD prophylaxis in matched related stem cell transplantation: Why post-transplant cyclophosphamide can be recommended a study by the EBMT transplant complications working party

Rabbit anti-thymocyte globulin (rATG) reduced chronic GVHD after matched related donor (MRD) allogeneic stem cell transplantation (alloSCT) from 69% to 32% in a randomized trial and is the recommended standard in Europe. Post-transplantation Cyclophosphamide (PTCy) is an emerging alternative but lacks such solid data in MRD alloSCT. We therefore analyzed outcomes of rATG (n = 4140) vs. PTCy (n = 1069) in adult patients with hematologic malignancies undergoing MRD alloSCT between 2017 and 2021 in the EBMT database. The provided hazard ratios (HR) and P-values are adjusted for potential risk factors using multivariate analysis. Results are given at 2 years after alloSCT for all endpoints except for acute GVHD (100 days). The main difference was a lower relapse incidence after PTCy vs. rATG (26.2% vs. 32.8%; HR 0.78 [CI 95%: 0.66-0.92], p = 0.003). Interaction analyses confirmed the consistency of this result across different disease risk index and conditioning intensity subgroups. Other major transplant outcomes showed no significant differences: non-relapse mortality, overall survival, progression-free survival, GVHD-free relapse-free survival, incidence and severity of acute GVHD as well as chronic GVHD. In summary, PTCy results in comparable GVHD and survival outcomes but lower relapse rates compared to rATG. We conclude that PTCy can be recommended in MRD alloSCT.