title: FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease.
abstract: On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. The approval was primarily based on the results of a randomized, double-blind trial in which 79 symptomatic patients with MCD were allocated (2:1) to siltuximab plus best supportive care (BSC) or to placebo plus BSC. The primary efficacy endpoint was the proportion of patients in each arm achieving a durable tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. Tumor response was based on independent review of CT scans using the revised Response Criteria for Malignant Lymphoma, and symptomatic response was defined as complete resolution or stabilization of 34 MCD-related signs and symptoms as reported by the investigator. Thirty-four percent of patients in the siltuximab arm and no patients in the placebo arm met the primary endpoint (P = 0.0012). The most common adverse reactions (>10% compared with placebo) during treatment with siltuximab were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.
authors.affiliation: Office of Hematology and Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. Albert.Deisseroth@fda.hhs.gov.
authors.forename: Albert
authors.initials: A
authors.lastname: Deisseroth
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Ko
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Lei
authors.initials: L
authors.lastname: Nie
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Jeanne F
authors.initials: JF
authors.lastname: Zirkelbach
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Julie
authors.initials: J
authors.lastname: Bullock
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Nitin
authors.initials: N
authors.lastname: Mehrotra
authors.affiliation: Office of Hematology and Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Pedro
authors.initials: P
authors.lastname: Del Valle
authors.affiliation: Office of Hematology and Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Haleh
authors.initials: H
authors.lastname: Saber
authors.affiliation: Office of Hematology and Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sheth
authors.affiliation: Office of Hematology and Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Brenda
authors.initials: B
authors.lastname: Gehrke
authors.affiliation: Office of Hematology and Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.affiliation: Office of Hematology and Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Ann
authors.initials: A
authors.lastname: Farrell
authors.affiliation: Office of Hematology and Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005871:Castleman Disease / Q000175:diagnosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008875:Middle Aged; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C504234:siltuximab