title: Tocilizumab for the treatment of steroid refractory graft-versus-host disease.
abstract: 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.
authors: Bone Marrow Transplant Program, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. wdrobysk@mcw.edu
authors: William R
authors: WR
authors: Drobyski
authors: Marcelo
authors: M
authors: Pasquini
authors: Kathy
authors: K
authors: Kovatovic
authors: Jeanne
authors: J
authors: Palmer
authors: J
authors: J
authors: Douglas Rizzo
authors: Ayman
authors: A
authors: Saad
authors: Wael
authors: W
authors: Saber
authors: Parameswaran
authors: P
authors: Hari
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000305:Adrenal Cortex Hormones; D061067:Antibodies, Monoclonal, Humanized; C502936:tocilizumab