Tocilizumab for the treatment of steroid refractory graft-versus-host disease. Biol Blood Marrow Transplant 2011 Dec;17(12):1862-8
Date
07/13/2011Pubmed ID
21745454Pubmed Central ID
PMC3716013DOI
10.1016/j.bbmt.2011.07.001Scopus ID
2-s2.0-81255163590 (requires institutional sign-in at Scopus site) 95 CitationsAbstract
Corticosteroid refractory graft-versus-host disease (GVHD) is one of the major challenges in the management of allogeneic stem cell transplant recipients. Although numerous agents have been employed to treat this patient population, no standardized second-line therapy exists. In this study, we report our experience with the administration of tocilizumab, an anti-interleukin 6 receptor antibody, in the treatment of steroid refractory GVHD. Tocilizumab was administered to 8 patients with refractory acute (n = 6) or chronic GVHD (cGVHD) (n = 2) once every 3 to 4 weeks. The majority of patients with acute GVHD (aGVHD) had grade IV organ involvement of the skin or gastrointestinal tract, whereas both patients with cGVHD had long-standing severe skin sclerosis at the time of treatment. There were no allergic or infusion-related adverse events. Treatment was discontinued in one patient over concerns that tocilizumab may have worsened preexisting hyperbilirubinemia. Several patients also had transient elevations in serum transaminase values. Infections were the primary adverse events associated with tocilizumab administration. Four patients (67%) with aGVHD had either partial or complete responses apparent within the first 56 days of therapy. One patient with cGVHD had a significant response to therapy, whereas the second had stabilization of disease that allowed for a modest reduction in immune suppressive medications. These results indicate that tocilizumab has activity in the treatment of steroid refractory GVHD and warrants further investigation as a therapeutic option for this disorder.
Author List
Drobyski WR, Pasquini M, Kovatovic K, Palmer J, Douglas Rizzo J, Saad A, Saber W, Hari PAuthors
William R. Drobyski MD Professor in the Medicine department at Medical College of WisconsinParameswaran Hari MD 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
MESH terms used to index this publication - Major topics in bold
Adrenal Cortex HormonesAdult
Aged
Antibodies, Monoclonal, Humanized
Cohort Studies
Drug Resistance
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Male
Middle Aged