Improved GVHD-free relapse-free survival when rATG/ATLG is used in allo-HCT from matched sibling donors - an EBMT registry study by the Transplant Complications Working Party

The EBMT recommends rabbit anti-thymocyte or anti-T-lymphocyte globulin (rATG/ATLG) as GVHD prophylaxis in matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). However, discrepancies between recommendations and clinical practice were reflected in the EBMT survey. Therefore, we performed retrospective EBMT registry analysis from 2014 to 2021 to reinforce the real-world evidence context of rATG/ATLG impact on post-transplantation outcomes. This study included 11,420 adult patients (non-ATG n = 7680 and ATG n = 3740) with hematological malignancies after the first allo-HCT from peripheral blood. Use of ATG was associated with a reduced risk of aGVHD II-IV (Day +100: non-ATG vs ATG, 27.6% vs. 21.6%; adjusted HR 0.7, p < 0.001) and cGVHD (2-year: non-ATG vs ATG, 48.9% vs 30%; adjusted HR 0.45, p < 0.001), improved OS (2-year: 62.9% vs 63.3%; adjusted HR 0.89, p = 0.009), reduced NRM (2-year: 16% vs 12.5%; adjusted HR 0.63, p < 0.001), and higher GRFS (2-year: 32.2% vs 40.7%; adjusted HR 0.72, p < 0.001). While RI was higher in the ATG group (2-year: non-ATG vs ATG, 30.2% vs 34.7%; adjusted HR 1.22, p < 0.001) it did not translate into a significantly lower PFS (2-year: 53.9% vs 52.8%; adjusted HR not significant). Overall, outcomes were favorable for the intermediate rATG/ATLG dose ranges compared to the low and high dose ranges. Administration of rATG/ATLG improved outcomes in MSD allo-HCT recipients, supporting the EBMT recommendation for its use.