Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 25042199 · doi:10.1016/S1470-2045(14)70319-5
What was done
A randomised, double-blind, placebo-controlled trial across 38 hospitals in 19 countries evaluated siltuximab (an anti-interleukin-6 chimeric monoclonal antibody) in HIV-negative and HHV-8-negative patients with symptomatic multicentric Castleman's disease. Participants were randomly assigned (2:1) to siltuximab (11 mg/kg IV every 3 weeks) plus best supportive care (n=53) or placebo plus best supportive care (n=26), stratified by baseline corticosteroid use, until treatment failure. The primary endpoint was durable tumour and symptomatic response for at least 18 weeks in the intention-to-treat population.
What was found
Durable tumour and symptomatic response occurred in 18 of 53 patients (34%) in the siltuximab group compared with 0 of 26 (0%) in the placebo group (difference 34.0%, 95% CI 11.1–54.8, p=0.0012). Grade 3 or higher adverse events occurred in 25 (47%) siltuximab patients vs 14 (54%) placebo patients; serious adverse events occurred in 12 (23%) vs 5 (19%), despite longer median treatment duration with siltuximab (375 days vs 152 days). Three patients (6%) in the siltuximab group experienced treatment-related serious adverse events (lower respiratory tract infection, anaphylactic reaction, sepsis).
Why it matters
This provides the first randomised controlled trial evidence for multicentric Castleman's disease, showing IL-6 blockade with siltuximab significantly improves tumor and symptom response compared to supportive care alone in HIV-negative, HHV-8-negative patients.
Limits
The sample size is relatively small (n=79), reflecting the rarity of the condition. The findings apply only to HIV-negative, HHV-8-negative patients and do not report overall survival data.
Cited by
- supports Tocilizumab is effective in approximately one-third of Castleman disease patients.