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.