Anti–IL-6 Antibody Siltuximab Produces Durable Responses in Multicentric Castleman's Disease


Key Points

  • Siltuximab produced tumor and symptomatic response for ≥ 18 weeks in 34% of patients vs 0% in patients receiving best supportive care alone.
  • Adverse event profiles were similar for siltuximab vs placebo despite longer siltuximab treatment duration.

Multicentric Castleman’s disease is characterized by overproduction of interleukin-6 (IL-6). In a trial reported in The Lancet Oncology, van Rhee et al found that the anti–IL-6 antibody siltuximab (Sylvant) produced a significantly better response rate vs placebo in patients with the disorder receiving best supportive care. 

Study Details

In this double-blind trial conducted at 38 hospitals worldwide, 79 HIV- and human herpesvirus-8–negative patients were randomly assigned 2:1 to receive siltuximab at 11 mg/kg via intravenous infusion every 3 weeks (n = 53) or placebo (n = 26) until treatment failure. The primary endpoint was durable tumor and symptomatic response for ≥ 18 weeks in the intention-to-treat population.

Response Rates

Durable tumor and symptomatic responses occurred in 18 patients (34%) in the siltuximab group and none (0%) in the placebo group (difference = 34.0%, 95% confidence interval = 11.1%–54.8%, P = .0012).

Adverse Events

Median treatment duration was longer in the siltuximab group (375 vs 152 days). The frequencies of grade 3 or higher adverse events (47% vs 54%) and serious adverse events (23% vs 19%) were similar in the two groups. The most common adverse events of grade 3 or higher were fatigue (9% vs 4%), night sweats (8% vs 4%), and anemia (2% vs 12%). Serious adverse events were considered related to siltuximab in 3 patients (6%; respiratory tract infection, anaphylactic reaction, sepsis).

The investigators concluded, “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.”

Frits van Rhee, MD, of University of Arkansas for Medical Sciences, is the corresponding author for The Lancet Oncology article.

The study was funded by Janssen Research & Development. For full disclosures of the study authors, visit

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