title: Siltuximab for multicentric Castleman disease.
abstract: Dysregulated secretion of IL-6 plays a pivotal role in the pathogenesis of Castleman disease (CD), a rare lymphoproliferative disorder. In contrast to unicentric CD for which surgery is considered the treatment of choice, there is no standard therapeutic approach for multicentric CD (MCD). Siltuximab (trade name: Sylvant, formerly known as CNTO 328) is a chimeric monoclonal antibody with high binding affinity for human IL-6. In a recent randomized placebo-controlled Phase II trial, subjects with HIV-negative, HHV8-negative MCD who received siltuximab demonstrated a significantly higher rate of durable tumor and symptomatic response with a tolerable safety profile, leading to its approval for the treatment of HIV-negative HHV8-negative MCD by the US FDA and the European Commission in April and May 2014, respectively. This article will cover the current treatment options of MCD, the drug profile of siltuximab and future directions in the management of MCD.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.
authors.forename: Yi-Chang
authors.initials: YC
authors.lastname: Liu
authors.forename: Katie
authors.initials: K
authors.lastname: Stone
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002097:C-Reactive Protein / Q000032:analysis; D005871:Castleman Disease / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D005260:Female; D006207:Half-Life; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D012372:ROC Curve; D019947:Receptors, Interleukin-6 / Q000737:chemistry / Q000378:metabolism; D016896:Treatment Outcome; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002097:C-Reactive Protein; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors; C504234:siltuximab
keywords: Castleman disease; IL-6; monoclonal antibody; siltuximab; targeted therapy