General Information

Sylvant (siltuximab) is an anti-interleukin-6 (IL-6) chimeric monoclonal antibody that binds to human IL-6.1 IL-6 is a multifunctional cytokine produced by various cells such as T-cells, B-cells, monocytes, fibroblasts and endothelial cells. Dysregulated overproduction of IL-6 from activated B-cells in affected lymph nodes has been implicated in the pathogenesis of, or mechanism causing, multicentric Castleman's disease.

Sylvant is specifically indicated for the treatment of patients with multicentric Castleman’s disease who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

Mechanism of Action

Sylvant (siltuximab) binds human IL-6 and prevents the binding of IL-6 to both soluble and membrane-bound IL-6 receptors. IL-6 has been shown to be involved in diverse normal physiologic processes such as induction of immunoglobulin secretion. Overproduction of IL-6 has been linked to systemic manifestations in patients with MCD.

Side Effects

Adverse effects associated with the use of Sylvant may include, but are not limited to, the following:

• pruritus
• increased weight
• rash
• hyperuricemia
• upper respiratory tract infection

Dosing/Administration

Sylvant is supplied as a solution for intravenous infusion. The recommended dose is 11 mg/kg is given over one hour as an intravenous infusion administered every three weeks until treatment failure.

Clinical Trial Results

The FDA approval of Sylvant was based on a phase I2, multinational, randomized, double-blind, placebo-controlled study. In this study, 53 subjects were randomized to best supportive care (BSC) and Sylvant at a dose of 11 mg/kg every three weeks and 26 subjects were randomized to BSC and placebo. Treatment was continued until treatment failure (defined as disease progression based on increase in symptoms, radiologic progression or deterioration in performance status) or unacceptable toxicity. The major efficacy outcome of the study was durable tumor and symptomatic response, defined as tumor response assessed by independent review and complete resolution or stabilization of MCD symptoms. A durable response was defined as tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. The durable tumor and symptomatic response in the Sylvant arm was 34 percent compared to 0 percent in the placebo arm (p=0.0012).