We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantat ion received tocilizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft-versus-host disease prophylaxis. Thirty-five patients were enrolled between January 2015 and June 2016. The median age of the cohort was 66 (range: 22-76). All patients received busulfan-based conditioning, and were transplanted with human leukocyte antigen-matched related or matched unrelated bone marrow or peripheral stem cell grafts. The cumulative incidences of grades II-IV and III-IV acute graft-versus-host disease were 14% (95% CI 5-30) and 3% (95% CI 0-11) at day 100, and 17% (95% CI 7-31) and 6% (95% CI 1- 16) at day 180, respectively. Notably, there were no cases of graft-versushost disease of the lower gastrointestinal tract within the first 100 days. A comparison to 130 matched controls who only received tacrolimus and methotrexate demonstrated a lower cumulative incidence of grades II-IV acute graft-versus-host disease (17% versus 45%, P=0.003) and a significant increase in grades II-IV acute graft-versus-host disease-free survival at six months (69% versus 42%, P=0.001) with tocilizumab, tacrolimus and methotrexate, which was the primary endpoint of the study. Immune reconstitution was preserved in patients treated with tocilizumab, tacrolimus and methotrexate, as T-cell and B-cell subsets recovered to near normal levels by 6-12 months post-transplantation. We conclude that tocilizumab has promising activity in preventing acute graft-versus-host disease, particularly in the lower gastrointestinal tract, and warrants examination in a randomized setting.
CITATION STYLE
Drobyski, W. R., Szabo, A., Zhu, F., Keever-Taylor, C., Hebert, K. M., Dunn, R., … Pasquini, M. (2018). Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft-versus-host disease: Low incidence of lower gastrointestinal tract disease. Haematologica, 103(4), 717–727. https://doi.org/10.3324/haematol.2017.183434
Mendeley helps you to discover research relevant for your work.