What is SYLVANT® (siltuximab)?
SYLVANT is the only therapy approved by the FDA for the treatment of people with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus (HIV) and human herpesvirus‑8 (HHV‑8).1,2
The National Comprehensive Cancer Network® (NCCN®) recommends using siltuximab as the first-line treatment for idiopathic multicentric Castleman disease (iMCD).3 SYLVANT is backed by the largest and most robust clinical studies in iMCD to date.1,4
SYLVANT works by neutralizing IL-6 in patients with iMCD1
SYLVANT works by binding directly to human interleukin-6 (IL-6) to prevent it from interacting with both soluble and membrane-bound IL-6 receptors.1 Increased IL-6 signaling is one of the established drivers of iMCD.5
In iMCD, excess amounts of a protein called IL-6 lead to overactivation of immune cells6,7
Abnormal IL-6 signaling may cause a cytokine storm that can lead to fever, night sweats, and unexplained weight loss, which are symptoms of iMCD8
SYLVANT was designed to target IL-6, preventing it from causing a cytokine storm and the symptoms associated with iMCD1
IL-6: An important signaling molecule that can become dysregulated in iMCD
Overproduction of IL-6 is a common pathological driver of iMCD5
IL-6 plays an important homeostatic role as part of the body’s immune system by regulating B cells and T cells9
IL-6 is a cytokine that is typically produced because of an infection or tissue damage9
IL-6 triggers B cells to produce antibodies in the germinal centers within the lymph nodes10
References: 1. SYLVANT [package insert]. Hertfordshire, UK: EUSA Pharma (UK) Ltd; 2019. 2. Mukherjee S, Martin R, Sande B, Paige JS, Fajgenbaum DC. Epidemiology and treatment patterns of idiopathic multicentric Castleman disease in the era of IL-6 directed therapy. Blood Adv. 2022;6(2):359-367. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.5.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed August 15, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. van Rhee F, Wong RS, Munshi N, et al. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014;15(9):966-974. 5. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124. 6. Fajgenbaum DC. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood. 2018;132(22):2323-2330. 7. van Rhee F, Stone K, Szmania S, Barlogie B, Singh Z. Castleman disease in the 21st century: an update on diagnosis, assessment, and therapy. Clin Adv Hematol Oncol. 2010;8(7):486-498. 8. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657. 9. Garbers C, Heink S, Korn T, Rose-John S. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov. 2018;17(6):395-412. 10. Choy EH, De Benedetti F, Takeuchi T, Hashizume M, John MR, Kishimoto T. Translating IL-6 biology into effective treatments. Nat Rev Rheumatol. 2020;16(6):335-345.