PTCy + ATG vs PTCy alone for GvHD prophylaxis in haplo-HSCT: A retrospective EBMT registry study

Graft-versus-host disease (GvHD) prophylaxis using post-transplant cyclophosphamide (PTCy) has substantially reduced the incidence of GvHD and non-relapse mortality in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The addition of antithymocyte globulin (ATG) to PTCy has shown further reductions in GvHD incidence in retrospective and non-comparative prospective studies.

Capes et al. conducted a large retrospective European Society for Blood and Marrow Transplantation (EBMT) registry study in patients with hematological malignancies (N = 5,194) receiving haplo-HSCT with peripheral blood stem cell grafts, comparing the efficacy of ATG + PTCy (n = 675) vs PTCy alone (n = 4,519) for GvHD prophylaxis. Results were published in the British Journal of Haematology. The median follow-up was 29.80 months. 

Key learnings

In univariate analysis, the PTCy only group showed higher 2-year RFS (50.9% vs 45.8%; p = 0.015), OS (56.9% vs 52.5%; p = 0.01), and cumulative incidence of cGvHD (28.4% vs 18.5%; p < 0.001) vs the PTCy + ATG group. 

In multivariable analysis, PTCy + ATG was associated with worse OS (HR, 1.18; p = 0.037) and RFS (HR, 1.18; p = 0.027) but lower cumulative incidence of cGvHD (HR, 0.68; p = 0.004) vs PTCy alone. 

A higher dose of ATG was associated with increased NRM (HR, 1.70; p = 0.024) and reduced extensive cGvHD (HR, 0.37; p = 0.038). 

In the context of haplo-HSCT, ATG + PTCy reduced cGvHD but worsened OS and RFS, particularly in patients with a high/very high DRI. Prospective trials are warranted to optimize treatment benefit and dosing strategies.