Steroids vs. steroids plus additional agent in frontline treatment of acute graft-versus-host disease: a systematic review and meta-analysis of randomized trials.

Publication Type:

Journal Article

Source:

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (2016)

Abstract:

Despite extensive research in the last few decades, progress in treatment of acute graft-versus-host disease (aGvHD), a common complication of allogeneic hematopoietic cell transplantation (HCT), has been limited and steroids continue to be the standard frontline treatment. Randomized clinical trials (RCTs) have failed to find a beneficial effect by escalating immunosuppression using additional agents. Considering the small number of RCTs, limited sample sizes, and frequent early termination due to anticipated futility, we conducted a systematic review and an aggregate data meta-analysis to explore whether a true efficacy signal has been missed due to the limitations of individual RCTs. Seven reports met our inclusion criteria. The control arm in all studies was 2 mg/kg/day prednisone (or equivalent). The additional agent(s) used in the experimental arm(s) were higher dose steroids, anti-thymocyte globulin, infliximab, anti- interleukin-2 receptor antibody (daclizumab and BT563), CD5-specific immunotoxin, and mycophenolate mofetil. Random effects meta-analysis revealed no efficacy signal in pooled response rates at various times points. Overall survival at 100 days was significantly worse in the experimental arm (relative risk 0.83, 95% confidence interval 0.74-0.94, P = 0.004, data from 3 studies) and showed a similar trend (albeit not statistically significantly) at 1 year as well (RR 0.86, 95%CI 0.68-1.09, P = 0.21, data from 5 studies). In conclusion, these results argue against the value of augmented generic immunosuppression beyond steroids for frontline treatment of aGvHD and emphasize the importance of developing alternative strategies. Novel forms of immunomodulation and targeted therapies against non-immune-related pathways may enhance the efficacy of steroids in this setting and early predictive and prognostic biomarkers can help identify the subgroup of patients that would likely need treatments other than (or in addition to) generic immunosuppression.