A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Hemoglobins
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Treatment Outcome

MeSH Major

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Giant Lymph Node Hyperplasia
  • Lymphoma, B-Cell
  • Multiple Myeloma

abstract

  • To evaluate the safety and pharmacokinetics of siltuximab, an anti-interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease. In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks. Response was assessed in all disease types. Clinical benefit response (CBR; composite of hemoglobin, fatigue, anorexia, fever/night sweats, weight, largest lymph node size) was also evaluated in Castleman disease. Sixty-seven patients received a median of 16 siltuximab doses for a median of 8.5 (maximum 60.5) months; 29 were treated 1 year or longer. There was no dose-limiting toxicity, antibodies to siltuximab, or apparent dose-toxicity relationship. The most frequently reported possible drug-related adverse events were thrombocytopenia (25%), hypertriglyceridemia (19%), neutropenia (19%), leukopenia (18%), hypercholesterolemia (15%), and anemia (10%). None of these events led to dose delay/discontinuation except for neutropenia and thrombocytopenia (n = 1 each). No treatment-related deaths occurred. C-reactive protein (CRP) suppression was most pronounced at 12 mg/kg every 3 weeks. Mean terminal-phase half-life of siltuximab ranged 17.73 to 20.64 days. Thirty-two of 37 (86%) patients with Castleman disease improved in 1 or more CBR component; 12 of 36 evaluable Castleman disease patients had radiologic response [complete response (CR), n = 1; partial response (PR), n = 11], including 8 of 19 treated with 12 mg/kg; 2 of 14 (14%) evaluable NHL patients had PR; 2 of 13 (15%) patients with multiple myeloma had CR. No dose-related or cumulative toxicity was apparent across all disease indications. A dose of 12 mg/kg every 3 weeks was recommended on the basis of the high response rates in Castleman disease and the sustained CRP suppression. Randomized studies are ongoing in Castleman disease and multiple myeloma. ©2013 AACR.

publication date

  • July 1, 2013

has subject area

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Female
  • Giant Lymph Node Hyperplasia
  • Hemoglobins
  • Humans
  • Lymphoma, B-Cell
  • Male
  • Middle Aged
  • Multiple Myeloma
  • Neoplasm Staging
  • Treatment Outcome

Research

keywords

  • Clinical Trial, Phase I
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-12-3349

PubMed ID

  • 23659971

Additional Document Info

start page

  • 3659

end page

  • 3670

volume

  • 19

number

  • 13