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Siltuximab: A Review in Idiopathic (Human Herpesvirus-8-Negative) Multicentric Castleman Disease

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Abstract

Siltuximab (Sylvant™), an interleukin (IL)-6 chimeric immunoglobulin Gк monoclonal antibody, is a currently the only agent approved to treat human idiopathic (herpesvirus-8 negative) multicentric Castleman disease (iMCD), which is a rare lymphoproliferative disorder. iMCD is caused by dysregulated production of IL-6 in the lymph nodes, and is associated with high morbidity, and potentially fatal consequences. Siltuximab binds to human IL-6 with high affinity and specificity, thereby preventing it from binding to IL-6 receptors, and neutralizing IL-6 bioactivity. In clinical trials in patients with iMCD, siltuximab reduced levels of C-reactive protein (a biomarker for IL-6), and provided clinical responses. Relative to placebo, the addition of siltuximab to best supportive care improved tumor- and symptom-related outcomes, with patients also reporting improvements in MCD symptoms, functional status, and well-being. Siltuximab has an acceptable tolerability profile, with the majority of treatment-emergent adverse events being manageable and/or of mild severity. In the absence of a cure, siltuximab represents a significant achievement in the management of this difficult-to-treat orphan disease.

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Acknowledgments

During the peer review process, the manufacturer of siltuximab was offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Katherine A. Lyseng-Williamson

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  1. Katherine A. Lyseng-Williamson
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Correspondence to Katherine A. Lyseng-Williamson.

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Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Katherine A. Lyseng-Williamson is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: D.R. Abernethy, US Food and Drug Administration, Silver Spring, MD, USA; H.E. El-Osta, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA; S. Saluja, Saran Ashram Hospital, Dayalbagh, Agra, India.

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Lyseng-Williamson, K.A. Siltuximab: A Review in Idiopathic (Human Herpesvirus-8-Negative) Multicentric Castleman Disease. BioDrugs 29, 399–406 (2015). https://doi.org/10.1007/s40259-015-0142-5

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  • DOI: https://doi.org/10.1007/s40259-015-0142-5

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