Research in context
Evidence before this study
We searched PubMed on Sept 1, 2019 for randomised trials comparing anti-thymocyte globulin to controls for the prevention of chronic graft-versus-host disease (GVHD) published from Jan 1 2006 until Sept 1, 2019. We used search terms “peripheral blood stem cell transplantation”; “bone marrow cell transplantation”; “antithymocyte globulin)”; “anti-t lymphocyte globulin grafalon”; “ATLG”; “clinical trial, phase iii OR “randomized controlled trial” separately and in various combinations. We found five randomised trials, four in patients receiving unrelated donor transplants and one in patients receiving sibling donor transplants. These five trials reported consistent results showing reductions in the incidence of chronic GVHD, and to a lesser extent, in acute GVHD.
Added value of this study
The present trial confirms the previously observed decrease in the incidence of chronic GVHD, but also shows improvements in patient-centred endpoints, such as a decrease in the need for immunosuppressive therapy, in symptoms associated with chronic GVHD, and depressive symptoms. These endpoints are in keeping with the 2006 and 2015 National Institute of Health (NIH) Consensus recommendations that primary and secondary endpoints of chronic GVHD treatment studies should focus on the clinical benefits of central importance to patients. Research groups continue to debate about appropriate primary endpoints for these trials; the need for immunosuppressive therapy at 2 years that we measured, parallels current chronic GVHD-free relapse-free survival and refractory chronic GVHD-free relapse-free survival in pinpointing benefits at longer timepoints of follow-up.
Implications for all the available evidence
The present trial showed an improvement in overall survival for patients receiving anti-thymocyte globulin, confirming a previous case control study that used the same brand and dose of antibody. These results contrast with those of the previous randomised studies, as mentioned. Available evidence suggests that both the dose and schedule of anti-thymocyte globulin administration are crucial. Improvements in anti-thymocyte globulin therapy will probably hinge on both dose finding studies, such as a paediatric study showing meaningful benefit from a lower dose, and the results of s that determine dose by recipient lymphocyte count, the major biological target of anti-thymocyte globulin.