Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease. Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Female
  • Humans
  • Interleukin-6
  • Male
  • Middle Aged
  • Young Adult

MeSH Major

  • Antibodies, Monoclonal
  • Giant Lymph Node Hyperplasia

abstract

  • 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. 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. 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). 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.

publication date

  • August 10, 2010

has subject area

  • Adult
  • Aged
  • Antibodies, Monoclonal
  • Female
  • Giant Lymph Node Hyperplasia
  • Humans
  • Interleukin-6
  • Male
  • Middle Aged
  • Young Adult

Research

keywords

  • Clinical Trial, Phase I
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1200/JCO.2009.27.2377

PubMed ID

  • 20625121

Additional Document Info

start page

  • 3701

end page

  • 3708

volume

  • 28

number

  • 23