Tocilizumab did not significantly reduce the incidence of grade II-IV acute GVHD although trends were seen in VUD recipients.
Addition of tocilizumab to standard GVHD prophylaxis did not improve long-term survival.
We determined the efficacy of tocilizumab (TCZ) in preventing grade II-IV acute GVHD (aGVHD) in patients with acute-leukemia or myelodysplasia undertaking matched-related-sibling (MSD) or volunteer-unrelated-donor (VUD) allogeneic-SCT after myeloablative or reduced-intensity conditioning across five Australian centers. 145 patients (50 MSD, 95 VUD) were randomly assigned to placebo or TCZ on day-1. All patients received T-cell-replete PBSC grafts and GVHD-prophylaxis with cyclosporin/methotrexate. A planned sub-study analyzed the VUD cohort. With a median follow up of 746 days, the incidence of grade II-IV aGVHD at day 100 for the entire cohort was 36% versus 27% for placebo versus TCZ (HR 0.69; CI:0.38-1.26, p=0.23) and 45% versus 32% (HR 0.61; CI:0.31-1.22, p=0.16) for the VUD subgroup. The incidence of grade II-IV aGVHD at day 180 for the entire cohort was 40% versus 29% for placebo versus TCZ (HR 0.68; CI:0.38-1.22, p=0.19) and 48% versus 32% (HR 0.59; CI:0.30-1.16, p=0.13) for the VUD subgroup. Reductions in aGVHD were predominantly in grade II disease. A trend to improved aGVHD-free survival (aGVHD-FS) was noted in the TCZ-treated VUD subgroup, 52% versus 68% for placebo versus TCZ (p=0.13). For the entire cohort, transplant-related-mortality occurred in 8% versus 11% of placebo versus TCZ-treated patients respectively (p=0.56) and overall-survival was 79% versus 71% (p=0.27). Median day to neutrophil and platelet engraftment was delayed by 2-3 days in TCZ-treated patients while liver toxicity and infectious complications were similar between groups. In this phase-3 randomized, double-blind trial (ACTRN12614000266662), tocilizumab showed non-significant trends to reduced incidence of grade II-IV aGVHD and improved aGVHD-FS in recipients of HLA-matched VUD donors, but no improvements in long term-survival.