BACKGROUND: 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.
METHODS: 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.
FINDINGS: 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).
INTERPRETATION: 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.
FUNDING: Janssen Research & Development.