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20-07-2014 | Article

Siltuximab Demonstrates Efficacy Against Multicentric Castleman’s Disease



medwireNews: A monoclonal antibody against interleukin (IL)-6 brings a treatment option for the rare lymphoproliferative disorder, multicentric Castleman’s disease, shows research.

The results of the first randomised clinical trial for the condition suggest that a siltuximab 11 mg/kg intravenous infusion at 3-week intervals plus best supportive care was well tolerated in patients despite prolonged exposure to the agent.

Moreover, 34% of the 53 patients assigned to receive siltuximab achieved both a durable tumour response and an improvement in symptoms, compared with none of the 26 patients who were given placebo plus best supportive care in the phase II trial.

“These results provide further evidence that interleukin 6 has a central role in development of multicentric Castleman's disease”, write Frits van Rhee, from the University of Arkansas for Medical Sciences in Little Rock, USA, and team in The Lancet Oncology.

“Based on these results, siltuximab has become the first treatment for HIV-negative, human herpesvirus-8-negative patients with multicentric Castleman's disease to be approved by the US Food and Drug Administration and the European Medicines Agency and is a valuable new treatment option.”

Patients assigned to receive siltuximab continued masked treatment for significantly longer than controls, at a median of 375 days versus 152 days, and discontinuation due to treatment failure occurred in 30% of siltuximab group and 54% of controls.

A tumour response was achieved by 38% of siltuximab-treated patients compared with just one (4%) control, a significant difference.

Siltuximab-treated patients achieved a greater improvement in median disease-related overall symptom score with each treatment cycle than controls and were significantly more likely to achieve a durable symptomatic response and a durable complete symptomatic response.

And at 1 year, all patients given siltuximab were alive compared with 92% of controls.

Of note, serious adverse events occurred in 23% of siltuximab treated patients and 19% of controls, with pruritus, maculopapular rash, weight gain, localised oedema and upper respiratory tract infection more common in the active treatment group. Grade 3 fatigue and night sweats were more common with siltuximab, whereas anaemia was more commonly experienced by controls.

“Multicentric Castleman's disease waxes and wanes, which was another justification for our placebo-controlled trial design, and the implementation of strict protocol definitions of treatment failure”, the researchers explain.

They suggest that some patients may have discontinued siltuximab too quickly or needed additional treatment, noting that activation of other cytokines, such as IL-1, IL-10 or tumour necrosis factor-alpha, plays a role in the disease.

“Future studies should address optimum treatment for patients with multicentric Castleman's disease, including combination treatments; however, siltuximab should be considered a valuable treatment option”, the team concludes.

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014

By Lynda Williams, Senior medwireNews Reporter