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Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial.

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机构： [1]Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA [2]Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China [3]Dana-Farber Cancer Institute, Boston, MA, USA [4]CHU de Montpellier, Hopital St Eloi, Montpellier, France [5]Peking University Third Hospital, Beijing, China [6]Oslo University Hospital, Oslo, Norway [7]North Shore Hospital, Takapuna Auckland, New Zealand [8]Hospital M鉫 de Deus, Porto Alegre, Brazil [9]West China Hospital, Sichuan University, Chengdu, China [10]Mackay Memorial Hospital, Taipei, Taiwan [11]Singapore General Hospital, Singapore [12]Beijing Cancer Hospital, Beijing, China [13]Seoul St Mary’s Hospital, Seoul, South Korea [14]Peking University First Hospital, Beijing, China [15]The Christie NHS Foundation Trust and University of Manchester, Manchester, UK [16]Janssen Research & Development, Spring House, PA, USA [17]Janssen Research & Development, Washington, GA, USA [18]Janssen Research & Development, Beerse, Belgium [19]Janssen Research & Development, Leiden, Netherlands [20]Fred Hutchinson Cancer Research Center, Seattle, WA, USA

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Multicentric Castleman's disease is a rare lymphoproliferative disorder driven by dysregulated production of interleukin 6. No randomised trials have been done to establish the best treatment for the disease. We assessed the safety and efficacy of siltuximab-a chimeric monoclonal antibody against interleukin 6-in HIV-negative patients with multicentric Castleman's disease. We did this randomised, double-blind, placebo-controlled study at 38 hospitals in 19 countries worldwide. We enrolled HIV-negative and human herpesvirus-8-seronegative patients with symptomatic multicentric Castleman's disease. Treatment allocation was randomised with a computer-generated list, with block size six, and stratification by baseline corticosteroid use. Patients and investigators were masked to treatment allocation. Patients were randomly assigned (2:1) to siltuximab (11 mg/kg intravenous infusion every 3 weeks) or placebo; all patients also received best supportive care. Patients continued treatment until treatment failure. The primary endpoint was durable tumour and symptomatic response for at least 18 weeks for the intention-to-treat population. Enrolment has been completed. The study is registered with ClinicalTrials.gov, number NCT01024036. We screened 140 patients, 79 of whom were randomly assigned to siltuximab (n=53) or placebo (n=26). Durable tumour and symptomatic responses occurred in 18 (34%) of 53 patients in the siltuximab group and none of 26 in the placebo group (difference 34·0%, 95% CI 11·1-54·8, p=0·0012). The incidence of grade 3 or more adverse events (25 [47%] vs 14 [54%]) and serious adverse events (12 [23%] vs five [19%]) was similar in each group despite longer median treatment duration with siltuximab than with placebo (375 days [range 1-1031] vs 152 days [23-666]). The most common grade 3 or higher were fatigue (five vs one), night sweats (four vs one), and anaemia (one vs three). Three (6%) of 53 patients had serious adverse events judged reasonably related to siltuximab (lower respiratory tract infection, anaphylactic reaction, sepsis). Siltuximab plus best supportive care was superior to best supportive care alone for patients with symptomatic multicentric Castleman's disease and well tolerated with prolonged exposure. Siltuximab is an important new treatment option for this disease. Janssen Research & Development. Copyright © 2014 Elsevier Ltd. All rights reserved.

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出版当年[2014]版：

大类 | 1 区

医学

小类 | 1 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区肿瘤学

第一作者：

第一作者机构： [1]Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA [*1]Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

通讯作者：

通讯机构： [1]Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA [*1]Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

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