Optimal GvHD prophylaxis in MSD transplantation: A network meta-analysis

Results from a prospectively registered systematic review and network meta-analysis (PROSPERO: 1290948) evaluating the comparative effectiveness of post-transplant cyclophosphamide (PTCy)-, antithymocyte globulin (ATG)-, and conventional calcineurin inhibitor (CNI)-based graft-versus-host disease (GvHD) prophylaxis in adults undergoing matched sibling donor (MSD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) were published in Transplantation and Cellular Therapy by Bentolila et al. The analysis included 860 MSD transplant recipients from six prospective randomized trials. 

Key data: In pooled direct comparisons vs conventional CNI-based prophylaxis, both PTCy- and ATG-based approaches improved GvHD-related outcomes, although with distinct clinical profiles. PTCy was associated with improved GvHD-free, relapse-free survival (GRFS; risk ratio [RR], 0.68; 95% confidence interval [CI], 0.56–0.82; p = 0.001) and a greater reduction in the risk of Grade 3–4 acute GvHD (aGvHD; RR, 0.36; 95% CI, 0.16–0.81; p = 0.014). Meanwhile, ATG was associated with greater reductions in the risk of any-grade chronic GvHD (cGvHD; RR, 0.48; 95% CI, 0.39–0.59; p < 0.001) and moderate-to-severe cGvHD (RR, 0.28; 95% CI, 0.17–0.44; p < 0.001). Indirect comparison showed no significant differences between PTCy and ATG for GRFS, overall survival (OS), relapse, or non-relapse mortality (NRM).  

Key learning: PTCy- and ATG-based prophylaxis offer broadly comparable overall clinical benefit in MSD transplantation, with complementary GvHD profiles favoring acute (PTCy) or chronic (ATG) GvHD prevention.