title: Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease.
abstract: OBJECTIVE
  Interleukin-6 (IL-6) has emerged as a key factor in the pathogenesis of the atypical lymphoproliferative disorder Castleman's disease (CD). Siltuximab is a new anti-IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD.
  
  
  METHODS
  We report interim results from an open-label, dose-finding, seven-cohort, phase I study in which patients with symptomatic, multicentric or unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals. The main efficacy end point of clinical benefit response (CBR) was defined as a composite of clinical and laboratory measures relevant to the management of CD. In addition, radiologic response was independently assessed by using modified Cheson criteria.
  
  
  RESULTS
  Eighteen (78%) of 23 patients (95% CI, 56% to 93%) achieved CBR, and 12 patients (52%) demonstrated objective tumor response. All 11 patients (95% CI, 72% to 100%) treated with the highest dose of 12 mg/kg achieved CBR, and eight patients (73%) achieved objective tumor response. Overall objective-response duration ranged from 44 to > or = 889 days, and one patient had complete response for > or = 318 days. Hemoglobin increased markedly in 19 patients (median increase, 2.1 g/dL; range, 0.2 to 4.7 g/dL) in the absence of transfusion or erythropoiesis-stimulating agents. No dose-limiting toxicity was reported, and only three patients had grade 3 or higher adverse events after a median exposure of 331 days (range, 1 to 1,148 days).
  
  
  CONCLUSIONS
  These interim results strongly suggest that siltuximab is an effective treatment with favorable safety for the management of CD. An additional study is planned to fully evaluate safety and efficacy at the recommended dose of 12 mg/kg every 3 weeks.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA. vanrheefrits@uams.edu
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
authors.forename: Peter
authors.initials: P
authors.lastname: Voorhees
authors.forename: Richard
authors.initials: R
authors.lastname: Furman
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Hossein
authors.initials: H
authors.lastname: Borghaei
authors.forename: Lubomir
authors.initials: L
authors.lastname: Sokol
authors.forename: Julie
authors.initials: J
authors.lastname: Crawford
authors.forename: Mark
authors.initials: M
authors.lastname: Cornfeld
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.forename: Xiang
authors.initials: X
authors.lastname: Qin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Herring
authors.forename: Corey
authors.initials: C
authors.lastname: Casper
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005871:Castleman Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; C504234:siltuximab