Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft-versus-host disease: low incidence of lower gastrointestinal tract disease. Haematologica 2018 Apr;103(4):717-727
Date
01/21/2018Pubmed ID
29351985Pubmed Central ID
PMC5865423DOI
10.3324/haematol.2017.183434Scopus ID
2-s2.0-85044420638 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation 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-versus-host 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.
Author List
Drobyski WR, Szabo A, Zhu F, Keever-Taylor C, Hebert KM, Dunn R, Yim S, Johnson B, D'Souza A, Eapen M, Fenske TS, Hari P, Hamadani M, Horowitz MM, Rizzo JD, Saber W, Shah N, Shaw B, Pasquini MAuthors
Anita D'Souza MD Associate Professor in the Medicine department at Medical College of WisconsinWilliam R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Mary Eapen MBBS, DCh, MRCPI, MS Professor in the Medicine department at Medical College of Wisconsin
Timothy Fenske MD Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
J. Douglas Rizzo MD, MS Director, Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Wael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Associate Professor in the Medicine department at Medical College of Wisconsin
Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAged
Antibodies, Monoclonal, Humanized
Drug Therapy, Combination
Female
Gastrointestinal Diseases
Graft Survival
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Immunosuppressive Agents
Incidence
Lower Gastrointestinal Tract
Male
Methotrexate
Middle Aged
Tacrolimus
Transplantation Conditioning
Young Adult
