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

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.